Clinical Genetics Leaflets

The leaflet is detailed below, or you can download the 'Predictive testing for a Breast Cancer 1(BRCA1) Gene alteration' leaflet in PDF.

Cancer is common in the general population with 1 in 2* people being diagnosed with a cancer in their lifetime. Approximately 1 in 7* women will be diagnosed with breast cancer and most cancer occurs just by chance.  Our suspicions of an inherited explanation for the cancers in a family are raised if the same or related cancers occur in several family members on the same side of the family, usually across different generations and at a younger age than expected. This is why genetic testing would be offered to a family.

*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

What are genes and chromosomes? 

Humans are made up of trillions of cells.  At the centre of almost all of your cells is a ball-shaped structure called the nucleus, inside of which are 46 thread-like structures called chromosomes. Chromosomes are long strands of DNA (DeoxyriboNucleic Acid). It is estimated that if a strand of DNA was stretched out, it would be around two meters long, even though the average cell is smaller than a pinhead.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

Image Source: https://cpmc.coriell.org

We have 23 pairs of chromosomes; one of each pair is inherited from your mother and one of each pair from your father. Chromosomes 1-22 are arranged in size order with number 1 being the largest and 22 the smallest. The 23^rd pair of chromosomes determines a person’s sex. Most males are XY and most females are XX. Chromosomes contain an estimated 20-30,000 pairs of genes that make us who we are. As we have pairs of chromosomes we therefore have pairs of genes.

Genes are often called the blueprint for life because they tell each of your cells what to do and when to do it. For example, some genes determine how tall you will be; some what colour your hair will be; some genes are responsible for maintenance in our bodies and some for our development, and so on. Genes do this by making proteins. In fact, each gene is really just a ‘recipe’ or a code for making a certain protein. In order for a gene to do the job it is supposed to do, the ‘recipe’ or code needs to be written correctly. If the ‘recipe’ is wrong, the protein is either not made, or is made incorrectly so cannot do the job it is supposed to do.  This is sometimes called a gene alteration, a spelling mistake or a gene mutation.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

What is the role of the BRCA1 gene?

The role of the BRCA1 gene is to protect the body against developing cancer in certain areas of the body. BRCA1 genes are called tumour suppressor genes and the protein produced from them helps prevent cells from growing and dividing too rapidly or in an uncontrolled way. The pair of BRCA1 genes is found on chromosome 17. 

What is the main cancer risks associated with having an altered BRCA1 gene?

*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

There may also be a small risk of developing other cancers but not enough to warrant additional screening. However, it would be important to have a low threshold for seeking medical help for any concerning or persistent symptoms.

What can be done to help manage these risks?

For each of the high risk cancers, screening and surgical options are discussed.  Different options are available to men and women, and options can also differ dependent on what age you are.

Breast Screening

Women who have a BRCA1 gene alteration are offered high risk breast screening. 

This involves:

• Annual magnetic resonance imaging (MRI) scan from 25-39 years
• Annual MRI AND mammography from 40-50 years
• Annual mammography from 51-71 years (some women may continue to receive MRI too)

Women who have a 50% chance of inheriting a BRCA1 gene alteration but choose not to have a genetic test will be offered the screening described above until the age of 50. These women will then need to have genetic testing in order to continue to receive high risk breast screening, otherwise they will join the NHS Breast Screening Programme for a mammogram every three years.

Most NHS routine or high risk breast screening stops after the age of 70 or in some places 73.  You can still have screening after this, and can arrange an appointment by contacting your local breast screening unit.  This is something we would recommend if you were a carrier of a BRCA1 gene alteration. We also suggest that women carry out monthly self-examination of the breasts.

Men are not offered any breast screening, but we suggest they check their chest and armpit areas and seek medical advice for any unusual lumps.

Breast Surgery

Women who have a BRCA1 gene alteration also have the option of having surgical removal of both breasts (bilateral mastectomy). Although this procedure could significantly reduce the risk of developing breast cancer it will not remove the risk entirely. We also recognise this is a radical step that requires careful consideration. Therefore women who choose this option are fully supported throughout the process and not rushed into making any decisions. 

Ovarian Screening and Surgery

Ovarian screening involves regular blood tests approximately 3-4 times a year, to measure a marker in the blood called CA125 and also by annual ultrasound from the age of 35. However, ovarian screening does not reliably inform us of cancers early enough in order for them to be treated effectively. 

Therefore, for women who are BRCA1 carriers, over the age of 35 and have completed their families we would encourage those to think about having their ovaries and fallopian tubes removed (bilateral salpingo-oophorectomy).  This can significantly decrease the risk of developing ovarian cancer but, again the risk of cancer is never removed entirely.

There are clear advantages to having your ovaries and fallopian tubes removed, however they do need to be weighed with the potential disadvantage of being put into an early menopause and the possible need for hormone replacement therapy (HRT).  The advantages and disadvantages of HRT could be further discussed with a gynaecologist if you choose to go ahead with this process.

Chemoprevention

Recent guidelines have suggested that ladies at high risk of breast cancer be offered chemo-prevention medications. Research suggests these medications can reduce the risk of developing breast cancer however they do have significant side effects. Please ask for a leaflet outlining the risks and benefits of chemoprevention if you think this is something you might be interested in. 

Prostate screening for people with a BRCA1 gene alteration

Prostate screening should be undertaken annually from the age of 40 in people who have a BRCA1 gene alteration. This can be provided through the GP.

How are BRCA1 gene alterations passed down (inherited) through families?

The way BRCA1 gene alterations are inherited is called DOMINANT inheritance. This is caused by an alteration in only one copy of the BRCA1 gene. Even though we each have 2 copies of the BRCA1 gene the normal copy cannot compensate for the altered copy and a person with one altered BRCA1 gene has an increased risk of developing cancer.

If a parent carries an altered BRCA1 gene, each of their children has a 50%, or 1 in 2 chance of inheriting the altered gene and therefore having an increased risk of developing cancer. For each child, regardless of their sex, the risk is the same = 50%.

pic 4

 

What is predictive testing?

Predictive testing is offered to family members who are known to be at risk of inheriting a gene alteration that has been identified in the family but are currently well. Predictive testing is usually offered over a series of appointments to allow the opportunity to consider options and choices with time for reflection in-between. How many appointments a person requires varies considerably from person to person and is negotiated on an individual basis with your genetic counsellor team. The overall aim of the predictive testing process is to help prepare you for your results whatever they are.

• What are the issues to think about when deciding whether or not to have a gene test?

A genetic test can establish whether you have an alteration in a gene which could affect your health. It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations and many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.

There are reasons for and against having a genetic test. Within one family, relatives often have different views. You should try to make your own decision, without feeling pressured from relatives or other influences.

You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor.

• How do you think you would cope if the test were to show that you have inherited the altered gene?

For some people, knowing that they have the altered gene is preferable to living with uncertainty. Having a genetic test enables them to make decisions about the future and about screening and measures to reduce their risk. Other people may prefer not to have the test because they may feel very anxious if the test shows that they have the altered gene.

• How do you think you would cope if the test were to show that you have not inherited the altered gene?

Perhaps surprisingly, it can often take people some time to get used to the knowledge that they do not have the altered gene. This can be particularly difficult when other relatives have a different result. People who do not have the altered gene have the same chance of developing cancer as other people in the general population.

• If the test were to show that you have the altered gene, this would mean that your children would also be at risk of having the altered gene. How do you think you might feel about this?

Having a genetic test may be important to other people, such as your children. It will help them to understand their own risk and if necessary make choices about screening and risk reducing options.                  It can be very difficult knowing that you could have passed on an altered gene to your children. This can be hard to deal with even if you know that you had no control over which genes you passed on.

• If you were to have the test, would you want to tell anyone the test results?

It is important to think about who you would want to know about your test as it is very personal information. Many people who attend our clinic find that it helps to confide in a partner, trusted friend or relative.

• Would having the test affect your ability to get life or medical insurance?

At present, if you have already obtained your insurance, having the test should not affect your current policies. However, it is not possible to know whether it will affect your ability to get or to change insurance policies in the future.

• Would having the test affect your employment?

If the test shows you have the altered gene it would be your decision whether or not to inform your present employers. Some employers might ask about this if you apply for a new job.

It is important that each family member makes the decision that is best for them. We will support you whether you decide to have the test or whether you decide against having the test. It is your decision!

• What happens if I choose to go ahead and have a test?

-After you have the opportunity to discuss the positives and negatives of predictive testing, if you wish to have the test you will be asked to read and sign a consent form and a small blood sample will then be taken.

- Once the blood is taken, the laboratory staff would test the sample to find out whether or not you have inherited the altered gene known in your family. 

Test results are usually available 4-6 weeks after having your blood taken and you can choose to have your results over the phone or in a clinic appointment.

IF, FOR SOME REASON YOU, HAVE NOT RECIEVED YOUR RESULTS WITHIN 4-6 WEEKS AS EXPECTED PLEASE CALL THE LIVERPOOL CENTRE FOR GENOMIC MEDICINE ON 0151 802 5008. Please remember to have your G number and W number handy for this call so we can quickly and correctly identify you.

• What Happens If I Choose Not To Go Ahead With Having A Test?

We may still recommend screening to you as explained earlier in this leaflet.

You can change your mind and decide not to have the test at any time before the result is given.

Other Factors to Consider

Insurance and Genetics

For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. The types of policy that require a medical history or genetic test are likely to be, life cover, critical illness insurance and income protection insurance.

We would suggest that if yourself or family members are considering taking out new insurance policies in the future that consideration be given to the possible affect genetic test results could have on the ability to gain insurance or the premiums charged. Genetic test results do not affect insurance policies already in place.

The Association of British Insurers (ABI) has a Code of Practice ‘The Concordat and Moratorium on Genetic and Insurance’.

• Insurance companies cannot ask for the Predictive Genetic Test results of individuals or family members (unless for Huntington Disease over £500,000). A Predictive Genetic Test is where an individual has a family member with a genetic condition, but who personally has no symptoms, signs or abnormal medical tests consistent with the condition at time of testing.
• If a family member has been diagnosed with a genetic condition based on a Diagnostic Genetic Test then you or family members will need to mention this when asked to provide your family’s medical history. In many cases Diagnostic Genetic Testing is used to confirm a diagnosis when a particular condition is suspected because of symptoms, signs or abnormal non-genetic tests including unusual findings on a routine blood test or other test.

Sources of further information on Insurance and Genetics:

The Association of British Insurers Genetics Frequently Asked Questions                        https://www.abi.org.uk/products-and-issues/topics-and-issues/genetics/genetics-faqs/

Genetic Alliance UK (Charity) Genetics & Insurance                           http://www.geneticalliance.org.uk/information/living-with-a-genetic-condition/insurance-and-genetic-conditions/

 

Family planning

Everyone who has an inherited genetic condition can choose from a variety of options to ensure they do not pass it on. It is a highly personal decision and there is certainly no expectation that couples have to do anything to prevent passing on a BRCA1 gene alteration, but for couples who wish to consider this, some of the choices can include:

• Preimplantation genetic diagnosis (PGD)

PGD involves the use of assisted reproductive technology (ART)|, which is also offered to couples with fertility problems. The aim is to obtain and fertilise a number of eggs. Once fertilised, the embryos develop for six days and then a number of cells are removed from each embryo. The genetic material (DNA or chromosomes) within each cell is then tested for the genetic or chromosome abnormality. Up to two unaffected embryos are then transferred to the uterus with the hope that they will implant and form a pregnancy. If successful, the baby should not be affected by the disorder it was tested for.

More information can be obtained here:  http://www.pgd.org.uk

• Adoption
• Sperm or egg donation: dependent on who carries the gene alteration.

Our experience is however that very few couples who carry a BRCA1 gene alteration choose any of the above options.

Oral Contraceptives

There have been a number of studies looking at the relationship between taking oral contraceptives and breast cancer risk but unfortunately the findings can often differ between different studies. However, overall, we know that taking the combined oral contraceptive pill (COC) increases the risk of breast cancer in all women. The risk appears to be confined to current and recent use and the risk drops once you stop taking the pill, and will return to normal after a number of years without use. It is felt that 10 years after stopping the COC, the breast cancer risk is the same as if you had never taken it at all.

One study showed an increased risk of breast cancer under the age of 40 to women who were carriers of a BRCA1 gene alteration (Narod SA et al (2002) Oral Contraceptives and the Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers, J Natl Cancer Inst 94:1773-9).

Use of COC also reduces the risk of ovarian cancer proportionally to the duration of use but should never be prescribed for this reason only.

There is no evidence regarding progesterone only contraceptives and breast cancer risk associated with family history.

You should discuss the use of oral contraceptives with your GP to weigh up the risks and benefits to help you make the decision that is right for you. You may also want to look at the Cancer Research UK website for further information.

 

 

Useful websites

Genetic Alliance UK                                                               www.geneticalliance.org.uk

Cancer research group UK (CRUK)                                      www.cruk.org.uk

National Institute for Health Care and Excellence (NICE)     www.nice.org.uk/Guidance/CG41

 

If you need more advice about any aspect of BRCA1 predictive testing, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008              Email: lwft.clingen@nhs.net

 

 

 

 

 

 

                                                                              

 

The leaflet is detailed below, or you can download the 'Information for men from families with a known alteration in the BRCA1 gene' leaflet in PDF.

Breast Cancer

In the UK, breast cancer affects 1 in 7* women during their lifetime. Most of these women are aged over 60. It is very rare for men to develop breast cancer. 

*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

Ovarian Cancer

Ovarian cancer is less common. In the UK, about 1 in 50* women are affected during their lifetime. Most of these women have been through the menopause.

*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

Prostate Cancer

It has been estimated that the lifetime risk of prostate cancer is around 1 in 6* for men in the UK. It is strongly related to age and very few men under the age of 50 will be diagnosed with prostate cancer. Around three quarters of cases occur in men over 65 years with the largest number diagnosed in those aged 75-79.

*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

What is inherited cancer?

In some families, women over several generations develop breast or ovarian cancer. Sometimes in these families men may also have had a prostate cancer. As this cancer is fairly common, especially in men over the age of 75, it may not be linked to breast or ovarian cancers. Occasionally men in these families have had breast cancer.

In a very small number of families some relatives may have inherited a gene alteration making them more likely to get cancer.

What are genes?

Our genes are the unique set of instructions inside our bodies which makes each of us individual. There are many thousands of different genes, each carrying a different instruction. As well as determining how we look, our genes control the way each cell or building block of the body works. Specific genes control specific cell types. Some genes are particularly important in controlling the way the cells in the breasts and ovaries grow. These genes may also be important in the growth of cells in the prostate.

We inherit two copies of each of our genes, one from our mother and one from our father.

Why do some genes increase the risk of cancer?

The instructions in each gene are like a code. Sometimes the code differs from that of a normal gene. For example imagine the normal code for a gene is:

1-2-3-4-5-6-7-8-9-10-11-12-13-14

The gene passed down through the family may have a slightly different code:

1-2-3-4-5-6-7-8-9-9-10-11-12-13-14

This gene will give slightly different instructions to the cells it controls than a gene with a normal code. We call this an altered gene.

If the altered gene is one that controls breast, ovarian and possibly prostate cells, there is a higher chance that breast, ovarian or prostate cancer may develop.

How can an altered gene be inherited?

If one parent (either the mother or the father) has an altered BRCA1 gene, this can be passed down to a child. Each child has a 50/50 chance of inheriting that parent's altered gene and a 50/50 chance of inheriting that parent's normal gene.

Which gene increases the risk of these cancers?

The two genes which we know are important in breast, ovarian and possibly prostate cancer when they are altered in this way are called BRCA1 and BRCA2. There may be other important genes which have not yet been discovered.

What if a man inherits an altered BRCA1 gene?

If a man inherits an altered BRCA1 gene his lifetime risk of developing prostate cancer is increased above the general population. He also has a slightly increased risk of developing breast cancer.

What screening is available for men who carry the altered gene, or who are at 50/50 risk of having the altered gene?

Although no breast screening is available to men with a BRCA1 gene alteration, we do advise that men check their breast and armpit area for any lumps and reports any concerns to their GP.

No screening test for prostate cancer has been shown to detect all cases of cancer and sometimes results of tests can be abnormal, even in men who do not have cancer. This can cause a great deal of anxiety as well as unnecessary investigations. However, if a man is found to be at increased risk of prostate cancer he can discuss screening with his GP who will advise him about what is available locally.

Prostate screening involves examination of the prostate and a blood test. To examine the prostate, the doctor inserts a finger into the back passage to check that the prostate is not enlarged. The blood test measures the level of a substance called PSA (Prostate Specific Antigen) that is raised in prostate cancer.

If you need more advice about any aspect of genetic testing for men, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

 

 

 

The leaflet is detailed below, or you can download the 'Genetic testing for BReast CAncer (BRCA) and PALB2 gene alterations' leaflet in PDF.

Introduction

Cancer is common in the general population with 1 in 2* people being diagnosed with a cancer in their lifetime, and most cancer occurs just by chance. Our suspicions of an inherited explanation for the cancers in a family are raised if the same or related cancers occur in several family members on the same side of the family, usually across different generations and at a younger age than expected. This is why genetic testing would be offered to a family.
*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

What are genes and chromosomes?

Humans are made up of trillions of cells. At the centre of almost all of your cells is a ball-shaped structure called the nucleus, inside of which are 46 thread-like structures called chromosomes. Chromosomes are long strands of DNA (DeoxyriboNucleic Acid). It is estimated that if a strand of DNA was stretched out, it would be around two meters long, even though the average cell is smaller than a pinhead.

 

 

 

Image Source: https://cpmc.coriell.org

We have 23 pairs of chromosomes and one of each pair is inherited from each of your parents. Chromosomes 1-22 are arranged in size order with number 1 being the largest and 22 the smallest. The 23rd pair of chromosomes determines a person’s sex. Most males are XY and most females are XX. Chromosomes contain an estimated 20-30,000 pairs of genes that make us who we are. As we have pairs of chromosomes we therefore have pairs of genes.
Genes are often called the blueprint for life because they tell each of your cells what to do and when to do it. For example, some genes determine how tall you will be; some what colour your hair will be; some genes are responsible for maintenance in our bodies and some for our development, and so on. Genes do this by making proteins. In fact, a gene may act by being a ‘recipe’ or a code for making a certain protein. In order for a gene to do the job it is supposed to do, the ‘recipe’ or code needs to be written correctly. If the ‘recipe’ is wrong, the protein is either not made, or is made incorrectly so cannot do the job it is supposed to do. This is sometimes called a gene alteration, a spelling mistake or a gene mutation.

 

 

 

 

What is the role of the BReast CAncer (BRCA) gene?

There are 2 BRCA genes that we know of and we all have 2 copies each of them. Our BRCA genes are known as BRCA1, which was the first BRCA gene to be identified, and BRCA2, which was the second BRCA gene to be identified. The role of our BRCA genes is to protect certain areas of the body from developing cancer. The BRCA genes are called tumour suppressor genes and the proteins produced from them help prevent cells from growing and dividing too rapidly or in an uncontrolled way. If there is an alteration in one of our BRCA genes then we have an increased susceptibility to developing cancer as we have less protection, but having an alteration in a BRCA gene does not mean a person will inevitably go on to develop cancer.

What is PALB2?

PALB2 is a gene that is known to be connected with breast cancer risk.

At present, if the cancers in a family are suggestive of having an alteration in one of the BRCA or PALB2 genes (the types of cancers associated with having a BRCA or PALB2 gene alteration are outlined in the tables below), we offer testing for alterations in these three genes. We are finding out about more genes all the time and it is possible that testing for different gene alterations may be available in the future.

What are the main cancer risks associated with having an altered BRCA gene?

There are slightly different cancer risks associated with having a BRCA1 or a BRCA2 gene alteration:

 

*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

 

There may also be a small risk of developing other cancers but not enough to warrant additional screening. However, it would be important to have a low threshold for seeking medical help for any concerning or persistent symptoms.

What are the main cancer risks associated with having an altered PALB2 gene?

 

What can be done to help manage these risks?
For each of the high risk cancers, screening and surgical options are discussed. Different options are available to men and women, and options can also differ dependent on what age you are.

Breast screening

Women who have a BRCA or PALB2 gene alteration are offered high risk breast screening. This involves:
• Annual magnetic resonance imaging (MRI) scan from 25-39 years
• Annual MRI AND mammography from 40-50 years
• Annual mammography from 51-71 years (some women may continue to receive MRI too)

Women who have a 50% chance of inheriting a BRCA gene alteration but choose not to have a genetic test will be offered the screening described above until the age of 50. These women will then need to have genetic testing in order to continue to receive high risk breast screening, otherwise they will join the NHS Breast Screening Programme for a mammogram every three years.

For women who have a 50% chance of inheriting a PALB2 gene alteration but do not want a genetic test, their level of breast screening is worked out based on their personal family history.

Most NHS routine or high risk breast screening stops after the age of 70 or in some places 73. You can still have screening after this, and can arrange an appointment by contacting your local breast screening unit. This is something we would recommend if you were a carrier of a gene alteration. We also suggest that women carry out monthly self-examination of the breasts.

Men are not offered any breast screening, but we suggest they check their chest and armpit areas and seek medical advice for any unusual lumps.

Breast surgery

Women who have a BRCA gene alteration also have the option of having surgical removal of both breasts (bilateral mastectomy). Although this procedure could significantly reduce the risk of developing breast cancer, it will not remove the risk entirely. We also recognise this is a radical step that requires careful consideration. Therefore women who choose this option are fully supported throughout the process and not rushed into making any decisions. A booklet entitled ‘Understanding risk-reducing breast surgery’ by Cancerbackup is available from us which outlines the types of surgery available and possible outcomes. Please do not hesitate to ask for one if you think this will be helpful.

What preventative surgery options are available for people with a PALB2 gene alteration?

We know that your risk of cancer will vary according to your family history. If you have a strong family history of breast cancer you may wish to consider preventative surgery of the breasts (also called risk reducing mastectomy). If you have a close relative affected with ovarian cancer then preventative removal of the ovaries may also be an option to consider. Please talk to your Genetic Counsellor or Clinical Geneticist if you would like to look into this further

Ovarian screening and surgery for people with a BRCA1 or BRCA2 gene alteration
Ovarian screening involves regular blood tests approximately 3-4 times a year, to measure a marker in the blood called CA125, and annual ultrasound scan from the age of 35. However, ovarian screening often does not reliably inform us of cancers early enough in order for them to be treated effectively. Therefore, for women who are BRCA gene alteration carriers, over the age of 35 and who have completed their families we would encourage them to think about having their ovaries and fallopian tubes removed (bilateral salpingo-oophorectomy). This can significantly decrease the risk of developing ovarian cancer and, also if undertaken around the age of 40, can reduce the risk of breast cancer. Again the risk of cancer is never removed entirely.

There are clear advantages to having your ovaries and fallopian tubes removed, however they do need to be weighed against the potential disadvantage of being put into an early menopause and the possible need for hormone replacement therapy (HRT). The advantages and disadvantages of HRT could be further discussed with a gynaecologist if you chose to go ahead with this process.

Chemoprevention

Recent guidelines have suggested that ladies at high risk of breast cancer can be offered chemo-prevention medications. Research suggests these medications can reduce the risk of developing breast cancer however they do have significant side effects. Please ask for a leaflet outlining the risks and benefits of chemoprevention if you think this is something you might be interested in.

Prostate screening for people with a BRCA1 or BRCA2 gene alteration

Prostate screening should be undertaken annually from the age of 40 in people who have a BRCA gene alteration. This can be provided through the GP.

How are BRCA and PALB2 gene alterations passed down (inherited) through families?

The way BRCA and PALB2 gene alterations are inherited is called DOMINANT inheritance. This is caused by an alteration in only one copy of the BRCA or PALB2 gene. Even though we each have 2 copies of the BRCA/PALB2 gene a normal copy cannot compensate for an altered copy and a person with one altered BRCA gene has an increased risk of developing cancer.

If a parent carries an altered BRCA or PALB2 gene, each of their children has a 50%, or 1 in 2 chance of having inherited the altered gene and therefore having an increased risk of developing cancer. For each child, regardless of their sex the risk is the same = 50:50

 

 

 

If I undergo testing for a BRCA or PALB2 gene alteration what will my results show?

Your results will show one of 3 things

1. A gene alteration is identified in your sample that is known to be disease causing (pathogenic). This is highly likely to be the reason for the cancers in the family. If you have had a cancer this is called diagnostic testing. It also means you remain at risk of developing other cancers associated with having a BRCA or PALB2 gene alteration. If you have not had a cancer it means that you now have a high risk of developing BRCA or PALB2 related cancers. Finding a gene alteration allows other family members to be offered predictive testing. Predictive testing is offered to family members who are known to be at risk of inheriting a gene alteration that has been identified in the family but are currently well. Predictive testing is usually offered over a series of appointments to allow the opportunity to consider options and choices with time for reflection in between. How many appointments a person requires varies considerably from person to person and is negotiated on an individual basis with your genetic counsellor team. The overall aim of the predictive testing process is to help prepare a person for their results, whatever they are.
   *NB: The finding of a pathogenic (disease causing) gene alteration is based on current knowledge. Very occasionally, new information in the future may mean that our understanding of the significance of a specific gene alteration may change*
2. 
   No gene alteration is identified. This does not mean there is not an inherited genetic explanation for the cancers in the family, but it may be that within the confines of current technology we have been unable to detect a gene alteration, or that there may be an alteration in a gene that we do not yet know about and, therefore, cannot test for. Regardless of the results of any genetic testing we may still make screening recommendations for family members based on the family history to help protect their health.
   For people who are undergoing genetic testing but who have NOT had a cancer: Please note that your result does not exclude the possibility that a BRCA or PALB2 gene alteration may be the responsible for the cancers in the family. Your result also DOES NOT provide any genetic information to anyone in the family apart from yourself and your children. In some circumstances we may be able to offer genetic testing to other family members as well. We will discuss this with you when we have your results.
3. 
   A gene change has been found but we are not sure if it is significant or not. This is also sometimes called an unclassified variant (UV) or a variant of unknown significance (VUS). Finding this may mean we have to undertake more testing in the family or that we may need to look at the UV again sometime in the future to see if any further information about it is available. This will be discussed with you in more detail should this be the case. 

What are the issues to think about when deciding whether or not to go ahead with genetic testing?

A genetic test can establish whether you have an alteration in a gene which could affect your health. It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations and many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.
There are reasons for and against having a genetic test. Within one family, relatives often have different views. You should try to make your own decision, without feeling pressured from relatives or other influences.
You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor. Some of the things people may consider include:

Do I need to tell people I am considering genetic testing?

It is entirely up to you whether or not you choose to tell anyone you are going ahead with genetic testing. It is often useful to have someone to accompany you to your appointments so that you have another ‘set of ears’ to hear the information and discussions that you have had. They can also be useful as a support for any discussions away from the appointment and should be someone you trust. People often choose this to be their partner, a close friend or another family member. However, if you choose to bring a family member it is important to remember the discussions you have in clinic are likely to have implications for them as well and they may not be prepared for this. Our experience, however, has demonstrated that families are often aware of the cancers and may already be asking questions about why and so it may be that an opportunity to discuss this within the family could happen quite naturally anyway.
Other people would rather wait until there is something to know before discussing things with the wider family, whilst other people prefer to discuss things as the process goes along to help prepare the family for any news. There are no right or wrong answers and we are happy to discuss how to involve your family if you wish.

Do my family need to know about any results I receive from genetic testing?

Genetic testing provides information for the individual but also will provide information for the rest of the family. If genetic testing identifies a gene alteration in you we would assume that you had inherited it from either your mother or father. Altered genes can often be passed down through families over generations without being noticed. Therefore, finding a gene alteration in you will have implications for other family members as well. So sharing genetic information in a family is really important. It can provide family members with a real opportunity to protect their health by enrolling in screening programmes to detect cancers as early as possible or even surgical options to help reduce the risk of developing cancer in the first place.
Sometimes people may think if genetic testing does not show anything then there is nothing to tell anyone. However, knowing what is happening in the family can prevent work being repeated as sometimes lots of family members are asking the same questions. It is also very important to remember that, regardless of the results of any genetic testing, the family history itself may mean family members are at a higher risk of cancer anyway and opportunities to protect their health can be offered to them.

How can I share this information?

On a practical level, you will have this leaflet to share with them and we will also provide a letter after your clinic appointment detailing any other issues discussed.
If a gene alteration is found we will provide you with a ‘relative’s letter’ detailing that a gene alteration has been identified in the family, that they are at risk and how to access testing. We will also guide you as to whom the letter should be passed on to.
On an emotional level, telling family members may be more difficult. You may be worried about upsetting them or have trouble deciding when the right time is. There really is no right or wrong answer to this but it is really useful to think about this before you get your test results and we are more than happy to discuss this with you further.

‘I won’t tell my children, it will only worry them.’

As parents, we want to protect our children from things that we believe can harm them and sometimes this means that we try and ‘hide’ things we think may be difficult for them to cope with. However, we tend to underestimate what children have already picked up on and they are often aware of something going on anyway. They may have noticed letters from the hospital or overheard conversations, they may also pick up cues from adults that they should not ask any questions.
Children in this situation may imagine something really awful is going on, often much worse than the reality, and may even believe it is something bad they have done.
Children value being included and are helped by adults who are honest and direct with communication. It is not always easy but children often cope a lot better than we give them credit for.
Our experience has also shown us that the parents of adult children often do the same. We are happy to talk to you about sharing information with your children during your appointment.

Who else should I tell?

That is entirely up to you. There is generally no obligation to tell your employer but it might be useful if you anticipate you may need time off work to have screening.
Having friends to discuss this with is helpful for some people but it is important to be aware that people may have differences of opinion that could be in conflict with any decisions you have made. However, for the majority of people, having discussions with other people is helpful and supportive.

What happens if I choose to go ahead and have a test?

After you have discussed what genetic testing could mean for you, you may decide to go ahead with testing. We will ask you to sign a consent form and we will take a blood sample from you.
The laboratory team will then search through the BRCA1, BRCA2 and PALB2 genes in your blood sample to see if the code in these genes differs from that of a normal gene. The BRCA1 and BRCA2 genes are large and can take a long time to be looked through. We would expect results to be ready in approximately 3-4 months but please remember sometimes it can be more and sometimes less.

 

You can discuss with your genetic counsellor or doctor how you wish to receive your results. Some people want their results by letter or by telephone with the opportunity of a follow-up appointment to discuss any findings, whereas others prefer to come into clinic to have the opportunity to discuss the implications of any findings and next steps. This is entirely up to you and will be discussed during your appointment.

IF, FOR SOME REASON YOU, HAVE NOT RECIEVED YOUR RESULTS WITHIN 3-4 MONTHS AS EXPECTED PLEASE CALL THE LIVERPOOL CENTRE FOR GENOMIC MEDICINE ON 0151 802 5008.

Please remember to have your G number and W number handy for this call so we can quickly and correctly identify you.

What happens if I choose not to go ahead with having a test?

If you choose not to have a test, we may still make screening recommendations for your relatives based on the family history of cancer. However, we will not be able to offer predictive testing to your relatives.
Attending clinical genetics does not oblige you to go ahead with testing and, if you do go ahead and change your mind about receiving your results, you can do so until you are ready.

Other factors to consider

Insurance and Genetics

For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. The types of policy that require a medical history or genetic test are likely to be, life cover, critical illness insurance and income protection insurance.

We would suggest that if yourself or family members are considering taking out new insurance policies in the future that consideration be given to the possible affect genetic test results could have on the ability to gain insurance or the premiums charged. Genetic Test results do not affect insurance policies already in place.

The Association of British Insurers (ABI) has a Code of Practice ‘The Concordat and Moratorium on Genetic and Insurance’:

• Insurance companies cannot ask for the Predictive Genetic Test results of individuals or family members (unless for Huntington Disease over £500,000). A Predictive Genetic Test is where an individual has a family member with a genetic condition, but who personally has no symptoms, signs or abnormal medical tests consistent with the condition at time of testing.
• If a family member has been diagnosed with a genetic condition based on a Diagnostic Genetic Test then you or family members will need to mention this when asked to provide your family’s medical history. In many cases Diagnostic Genetic Testing is used to confirm a diagnosis when a particular condition is suspected because of symptoms, signs or abnormal non-genetic tests including unusual findings on a routine blood test or other test.

Sources of Further Information on Insurance and Genetics:

The Association of British Insurers Genetics Frequently Asked Questions https://www.abi.org.uk/products-and-issues/topics-and-issues/genetics/genetics-faqs/
Genetic Alliance UK (Charity) Genetics & Insurance http://www.geneticalliance.org.uk/information/living-with-a-genetic-condition/insurance-and-genetic-conditions/

 

Useful Websites

Genetic Alliance UK www.geneticalliance.org.uk
Cancer Research group UK (CRUK) www.cruk.org.uk
National Institute for Health Care and Excellence (NICE) www.nice.org.uk/Guidance/CG41

All images in this leaflet were provided by NHS National Genetics and Genomics Education Centre

 

 

All images in this leaflet were provided by NHS National Genetics and Genomics Education Centre

The leaflet is detailed below, or you can download the 'Information for men from families with a known alteration in the BRCA2 gene' leaflet in PDF.

Breast Cancer

In the UK, breast cancer affects 1 in 7* women during their lifetime. Most of these women are aged over 60. It is very rare for men to develop breast cancer. 

*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

Ovarian Cancer

Ovarian cancer is less common. In the UK, about 1 in 50* women are affected during their lifetime. Most of these women have been through the menopause.

*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

Prostate Cancer

It has been estimated that the lifetime risk of prostate cancer is around 1 in 6* for men in the UK. It is strongly related to age and very few men under the age of 50 will be diagnosed with prostate cancer. Around three quarters of cases occur in men over 65 years with the largest number diagnosed in those aged 75-79.

*Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

What is inherited cancer?

In some families, women over several generations develop breast or ovarian cancer. Sometimes in these families men may also have had a prostate cancer. As this cancer is fairly common, especially in men over the age of 75, it may not be linked to breast or ovarian cancers. Occasionally men in these families have had breast cancer.

In a very small number of families some relatives may have inherited a gene alteration making them more likely to get cancer.

What are genes?

Our genes are the unique set of instructions inside our bodies which makes each of us individual. There are many thousands of different genes, each carrying a different instruction. As well as determining how we look, our genes control the way each cell or building block of the body works. Specific genes control specific cell types. Some genes are particularly important in controlling the way the cells in the breasts and ovaries grow. These genes may also be important in the growth of cells in the prostate.

We inherit two copies of each of our genes, one from our mother and one from our father.

Why do some genes increase the risk of cancer?

The instructions in each gene are like a code. Sometimes the code differs from that of a normal gene. For example imagine the normal code for a gene is:

1-2-3-4-5-6-7-8-9-10-11-12-13-14

The gene passed down through the family may have a slightly different code:

1-2-3-4-5-6-7-8-9-9-10-11-12-13-14

This gene will give slightly different instructions to the cells it controls than a gene with a normal code. We call this an altered gene.

If the altered gene is one that controls breast, ovarian and possibly prostate cells, there is a higher chance that breast, ovarian or prostate cancer may develop.

How can an altered gene be inherited?

If one parent (either the mother or the father) has an altered BRCA2 gene, this can be passed down to a child. Each child has a 50/50 chance of inheriting that parent's altered gene and a 50/50 chance of inheriting that parent's normal gene.

Which gene increases the risk of these cancers?

The two genes which we know are important in breast, ovarian and possibly prostate cancer when they are altered in this way are called BRCA1 and BRCA2. There may be other important genes which have not yet been discovered.

What if a man inherits an altered BRCA2 gene?

If a man inherits an altered BRCA2 gene his lifetime risk of developing prostate cancer is increased up to 20%. He also has a slightly increased risk of developing breast and possibly other cancers. 

What screening is available for men who carry the altered gene, or who are at 50/50 risk of having the altered gene?

Although no breast screening is available to men with a BRCA2 gene alteration, we do advise that men check their breast and armpit area for any lumps and report any concerns to their GP.

No screening test for prostate cancer has been shown to detect all cases of cancer and sometimes results of tests can be abnormal, even in men who do not have cancer. This can cause a great deal of anxiety as well as unnecessary investigations. However, if a man is found to be at increased risk of prostate cancer he can discuss screening with his GP who will advise him about what is available locally.

Prostate screening involves examination of the prostate and a blood test. To examine the prostate, the doctor inserts a finger into the back passage to check that the prostate is not enlarged. The blood test measures the level of a substance called PSA (Prostate Specific Antigen) that is raised in prostate cancer.

If you need more advice about any aspect of genetic testing for men, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

 

 

 

 

 

 

If you need more advice about any aspect of genetic testing for men, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008              Email: lwft.clingen@nhs.net

The leaflet is detailed below, or you can download the 'Dominant Inheritance' in PDF.

What are genes?

Genes are the unique set of instructions inside our bodies which make each of us an individual. There are many thousands of different genes, each carrying a different instruction. If a gene is altered, it can cause a genetic condition or disease. This gene alteration is sometimes known as a mutation.

We have two copies of each gene. One copy is inherited from each of our parents. When we have children, we pass on only one copy of each of our genes.

What does dominant inheritance mean?

Some genetic conditions are passed on in the family in a dominant way. These conditions are caused by an alteration in one copy of a gene. They are called dominant because the altered copy of the gene is dominant over the other copy of the gene.

Having children

If a parent carries an altered gene for a dominant condition, each of their children has a 50%, or 1 in 2 chances of inheriting the altered gene and being affected by the condition. For each child, regardless of their sex, the risk is the same = 50%.

In some dominant conditions, it is possible to inherit an altered gene without showing any symptoms of the condition. Even within a family, some individuals may be affected by the same dominant condition in different ways.

Some dominant conditions are known as "late onset disorders". In other words, they only affect individuals in adulthood.

In some families, an isolated case of a dominant disorder may be the result of a new mutation (a change which arises for the first time) in either the egg or the sperm that went to make that child.

 

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

 

If you need more advice about any aspect of Dominant Inheritance, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008              Email: lwft.clingen@nhs.net

 

 

 

 

 

 

 

 

 

 

If you need more advice about any aspect of Dominant Inheritance, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

The leaflet is detailed below, or you can download the 'Familial Adenomatous Polyposis (FAP) in the family' in PDF.

What is Familial Adenomatous Polyposis (FAP)?

FAP is a condition which runs in families, hence the term "familial". The rest of the name comes from the fact that little lumps called polyps, grow in large numbers on the lining of the bowel. The polyps themselves are not cancerous, but people who have FAP will eventually develop cancer if they do not receive treatment.

What is a polyp?

Polyps are non-cancerous lumps, or tumours, which grow on the surface of the bowel. There are many different kinds of polyp which grow in a number of places in the body, but the polyps we see in the bowel of people with FAP are called adenomas. Bowel polyps are found in many people without FAP, but usually just a few polyps are found. A diagnosis of FAP is made when large numbers of adenomas are found in the large bowel, which is the end of the long food pipe of the body which we call the colon and rectum. The following diagram shows where the colon and rectum are in the body, and what the polyps look like inside the bowel.

 

How is FAP inherited?

FAP is due to a fault in a gene that can be passed down families form a parent to their child. Genes are messages which control the working of the body and decide things like the colour of our eyes. Think of genes as recipes. The recipes allow the body to make chemical tools and building blocks. If part of the recipe is missing or has been copied incorrectly, that part of the body will not be able to do its job properly.

Most genes come in matching pairs, with a copy of each gene coming from the mother’s egg and a copy from the father's sperm. We think that everyone has at least one gene which doesn't work, but usually the spare copy from the other parent is enough to get by on. Some genes seem to be so important that you need both copies working to remain healthy. One faulty copy of a gene of this type can cause disease, so we call this gene dominant because it shows itself despite the presence of a normal copy.

FAP is one of the more frequent dominant genetic problems, but it is still uncommon, affecting about one person in every 8,000.

If someone has FAP it means that they have a working copy and a faulty copy of the gene. Each time they have a child there is a 50:50 chance that they will pass on the working copy and a fifty-fifty chance that they will pass on the faulty copy.

How do we know who has FAP?

Most people who have the gene for FAP begin to develop polyps in the colon in their early teens, so bowel checks should start between 10 and 14 years of age. Most people with FAP have developed polyps by the age of 30, and with every passing year without polyps, the likelihood that they have inherited the working copy of the gene increases.

The FAP gene has other effects on the body as well as causing polyps to appear. Some people get skin cysts, and some get harmless bumps on their bones.

For some reason, which we don't understand, most people get small black dots at the back of the eye which we call CHRPEs (this stands for congenital hypertrophy of the retinal pigment epithelium, but no-one ever calls them that!). These do not affect vision in any way. A lot of people who do not have FAP have one or two of these black dots, but if there are more than five, or a large distinctive area, then this is a good indication that the person carries the FAP gene. If CHRPEs do not run in your family with polyps, then a clear eye examination does not mean that you do not carry the gene. There are different ways we can decide who has FAP; look for polyps, look for CHRPEs, do gene tests, or look for bony lumps or cysts.

The only way we can be sure that anyone has FAP is if we find a lot of polyps, or if we can prove that a person carries a faulty copy of the gene.

Gene Tests

If we think of a gene as a long word carrying a message, then the FAP gene has nearly 9000 letters in it. In different families it is a different letter or group of letters which have been wrongly copied which causes the gene not to work. The genetics team will try to work this out for each family, and if we find the "spelling" mistake we will offer a test to the rest of the family to find out who has it and who has not.

Blood cells contain copies of all your genes, so we can test the FAP gene from a blood sample. If a blood sample is not possible, saliva or other samples can sometimes be used.

Those who do not have the faulty copy of the gene can stop bowel screening, and they cannot pass FAP to their children. Those who do have the faulty copy will continue with regular screening as before, until polyps are found.

For some families we cannot offer a gene test. This may be because we have not yet found the fault in the gene in that family, or it may be that no one is available who has FAP to test. If no gene test can be done, you will be advised to carry on with regular bowel checks.

Looking for polyps

A short tube can be passed through the back passage into the lower part of the bowel. This examination is called a sigmoidoscopy, and you will be able to go home from hospital on the same day.

A longer, flexible tube can be used to examine more of the bowel, and this procedure is called a colonoscopy.

Doctors may use either method, but for colonoscopy, it is necessary to prepare the bowel by emptying it before the test. The hospital will give you details about this, but it usually involves taking a liquid medicine the day before the check, and sticking to a low bulk diet for a few days to ensure that the bowel is quite empty.

What happens if polyps are found?

Usually the doctor will take a sample of the lining of the bowel, or from a polyp, to be examined under the microscope. If these are harmless, it is sometimes reasonable to carry on with regular checks. However, most doctors offer the choice of having an operation if they find a large number of polyps. Many people choose to have an operation as soon as polyps are found, rather than wait until there are large polyps.

The three main operations to remove the colon are:-

An Ileo-rectal anastomosis (IRA) involves removing the large bowel and attaching the small bowel to the rectum. This allows you to go to the toilet normally, but sometimes this can be many times a day. The rectum, which remains intact, may develop polyps so this must be examined at least once a year to prevent a cancer starting there.

A pouch operation involves the removal of the lining of the rectum when the colon is removed. A pouch is then made from the end of the small bowel, which then takes over some of the work of the colon. No checks have to be made on the rectum as there is no lining to grow polyps.

A pan-procto colectomy is done when the rectum has to be removed. The end

of the small bowel is brought to the surface and the waste material is collected in a disposable bag.

Where else could problems occur?

People with FAP also develop polyps in the small intestine. Screening by endoscope from 25 will detect polyps and guide further management. Between 4 and 12% of patients develop cancer of the small intestine.

Is there a cure?

Research is ongoing to try to develop new treatments.

Doctors are also looking at non-surgical ways to stop polyps growing, such as drug treatment, and these may be recommended in certain circumstances.

These options may offer an opportunity to treat polyposis without surgery in the

future but the only safe option at the moment is an operation.

Explanation of unfamiliar words:

FAMILIAL Something which runs in families.

POLYP A non-cancerous lump on the bowel wall.

 ADENOMA  (Adenomatous) There are different kinds of polyp: this describes how the polyps in FAP look under the microscope.

LARGE BOWEL The end section of the intestine or food pipe made up of colon and rectum.

GENE One of the chemical recipes which control the working of the body.

DOMINANT Only one of a pair of genes is faulty.

CHRPE (Congenital hypertrophy of retinal pigment epithelium). Harmless black marks on the back of the eye.

SIGMOIDOSCOPY A short tube with a light at the end is passed into the rectum and the last part of the colon to look for polyps.

COLONOSCOPY Like sigmoidoscopy, but the whole colon is seen.

APC The name scientists give the FAP gene. It stands for adenomatous polyposis coli.

COLECTOMY An operation to remove the colon, leaving the rectum in place.

ILEO-RECTAL ANASTAMOSIS (IRA) The small bowel is attached to the rectum when the colon has been removed.

POUCH A similar operation to IRA but the lining of the rectum is also removed and is replaced by lining from the small bowel.

PAN-PROCTO COLECTOMY (PPC) The colon and rectum are removed and the small bowel is brought to the surface of the abdomen.

ILEOSTOMY When someone has a PPC operation, the waste material is collected in a disposable bag.

DESMOID  A non cancerous tumour which may grow in the abdomen leading to pain and obstruction.

Who should I contact for further advice?

The first person you should ask if you have any health problems is your family doctor. It may be that he/she is not very familiar with this problem, so you should take along this fact sheet. If anyone in your family has FAP, then they will have a surgeon, and you could ask them for advice. Every region in the UK has a genetics service and they can be contacted for help via your GP or directly for advice.

If you need more advice about any aspect of FAP, you are welcome to contact:

Cheshire and Merseyside Clinical Genetics Service

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

 

Telephone 0151 802 5003 or 5008

 

Facsimile: 0151 702 4286

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The leaflet is detailed below, or you can download the 'Genetic Testing for Lynch Syndrome' in PDF.

Introduction

Cancer is common in the general population with 1 in 2* people being diagnosed with a cancer in their lifetime and most cancer occurs just by chance.  Our suspicions of an inherited explanation for the cancers in a family are raised if the same or related cancers occur in several family members on the same side of the family, usually across different generations and at a younger age than expected. This is why genetic testing would be offered to a family. 

*Cancer research UK (2015) Estimated Lifetime Risk of being diagnosed, people born after 1960.

What are genes and chromosomes?

Humans are made up of trillions of cells.  At the centre of almost all of your cells is a ball-shaped structure called the nucleus, inside of which are 46 thread-like structures called chromosomes. Chromosomes are long strands of DNA (DeoxyriboNucleic Acid). It is estimated that if a strand of DNA was stretched out, it would be around two meters long, even though the average cell is smaller than a pinhead.

 

 

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

 

 Image Source: https://cpmc.coriell.org

We have 23 pairs of chromosomes; one of each pair is inherited from your mother and one of each pair from your father. Chromosomes 1-22 are arranged in size order with number 1 being the largest and 22 the smallest. The 23^rd pair of chromosomes determines a person’s sex. Most males are XY and most females are XX. Chromosomes contain an estimated 20-30,000 pairs of genes that make us who we are. As we have pairs of chromosomes we therefore have pairs of genes.

Genes are often called the blueprint for life because they tell each of your cells what to do and when to do it. For example, some genes determine how tall you will be; some what colour your hair will be; some genes are responsible for maintenance in our bodies and some for our development, and so on. Genes do this by making proteins. In fact, a gene may act by being a ‘recipe’ or a code for making a certain protein. In order for a gene to do the job it is supposed to do, the ‘recipe’ or code needs to be written correctly. If the ‘recipe’ is wrong, the protein is either not made, or is made incorrectly so cannot do the job it is supposed to do.  This is sometimes called a gene alteration, a spelling mistake or a gene mutation.

Diag C

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

What is Lynch Syndrome?

Lynch syndrome is a hereditary condition that causes people to have an increased risk of developing certain types of cancer and is caused by a gene alteration. Lynch syndrome also used to be known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC).                                                                                 

What genes are associated with Lynch Syndrome?

There are currently 4 genes that we know of that, if they are altered, can be associated with the development of Lynch syndrome. These genes are known as MLH1, MSH2, MSH6 and PMS2. In fact we all have 2 copies each of these genes and they have a very important role to protect certain parts of our body from developing cancer. These genes are called mis-match repair genes and help protect us from developing cancer by detecting and correcting errors that can occur in DNA when cells copy themselves (DNA replication errors). They are like a quality control system that will either repair the mistakes in the DNA or gets rid of the cell with the mistake to stop it being copied anymore. If there is an alteration in one of our Lynch syndrome genes this quality control system is less effective and the person then has an increased susceptibility to developing cancer. But having an alteration in a Lynch syndrome gene does not mean a person will definitely go on to develop cancer.

What are the main cancer risks associated with having a Lynch Syndrome gene alteration?

There is a high risk of bowel cancer, with women having the additional risk of gynecological cancers including endometrial (womb) and ovarian cancer.  Each of the genes associated with Lynch Syndrome carry different cancer risks.

There may also be a small risk of developing other cancers including kidney (renal) cancer and pancreatic cancer but not enough to warrant routine screening unless there is a family history.

What can be done to help manage these risks?

Symptom awareness, aspirin use, screening or surgical options may be suitable. Different options are available to men and women, and options can also differ dependent on what age you are.

Choices and options will be discussed in detail if genetic testing shows you have Lynch Syndrome.

How Lynch Syndrome gene alterations are passed down (inherited) through families?

The way Lynch syndrome gene alterations are inherited is called DOMINANT inheritance. This is caused by an alteration in only one copy of a Lynch syndrome gene. Even though we each have 2 copies of Lynch syndrome genes a normal copy cannot compensate for an altered copy and a person with one altered Lynch syndrome gene has an increased risk of developing cancer.

If a parent carries an altered Lynch syndrome gene, each of their children has a 50%, or 1 in 2 chance of having inherited the altered gene and therefore having an increased risk of developing cancer. For each child, regardless of their sex the risk is the same = 50:50.

Diag D

 

 

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

If I undergo testing for a Lynch syndrome gene alteration what will my results show?

Your results will show one of 3 things:

1. A gene alteration is identified in your sample that is known to be disease causing (pathogenic). This is highly likely to be the reason for the cancers in the family. If you have had a cancer this is called diagnostic testing. It also means you remain at risk of developing other cancers associated with having a Lynch syndrome gene alteration.  Finding a gene alteration allows other family members to be offered predictive testing. Predictive testing is offered to family members who are known to be at risk of inheriting a gene alteration that has been identified in the family but are currently well. Predictive testing is usually offered over a series of appointments to allow the opportunity to consider options and choices with time for reflection in-between. How many appointments a person requires varies considerably from person to person and is negotiated on an individual basis with your genetic counsellor team. The overall aim of the predictive testing process is to help prepare a person for their results whatever they are.
2. No gene alteration is identified. This does not mean there is not an inherited genetic explanation for the cancers in the family but it may be that within the confines of current technology we have been unable to detect a gene alteration or, that there may be an alteration in a gene that we do not yet know about and, therefore, cannot test for. Regardless of the results of any genetic testing we may still make screening recommendations for family members based on the family history to help protect their health.
3. A gene change has been found but we are not sure if it is significant or not. This is also sometimes called an unclassified variant (UV) or a variant of unknown significance (VUS). Finding this may mean we have to undertake more testing in the family or that we may need to look at the UV again sometime in the future to see if any further information about it is available. This will be discussed with you in more detail should this be the case.

*NB: The finding of a pathogenic (disease causing) gene alteration is based on current knowledge. Very occasionally, new information in the future may mean that our understanding of the significance of a specific gene alteration may change.*

What are the issues to think about when deciding whether or not to go ahead with genetic testing?

A genetic test can establish whether you have an alteration in a gene which could affect your health. It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations and many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.

There are reasons for and against having a genetic test. Within one family, relatives often have different views. You should try to make your own decision, without feeling pressured from relatives or other influences.

You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor. Some of the things people may consider include:

• Do I need to tell people I am considering genetic testing?

It is entirely up to you whether or not you choose to tell anyone you are going ahead with genetic testing. It is often useful to have someone to accompany you to your appointments so that you have another ‘set of ears’ to hear the information and discussions that you have had. They can also be useful as a support for any discussions away from the appointment and should be someone you trust. People often choose this to be their partner, a close friend or another family member. However, if you choose to bring a family member it is important to remember the discussions you have in clinic are likely to have implications for them as well and they may not be prepared for this.  Our experience, however, has demonstrated that families are often aware of the cancers and may already be asking questions about why and so it may be that an opportunity to discuss this within the family could happen quite naturally anyway.

Other people would rather wait until there is something to know before discussing things with the wider family, whilst other people prefer to discuss things as the process goes along to help prepare the family for any news. There are no right or wrong answers and we are happy to discuss how to involve your family if you wish.

• Do my family need to know about any results I receive from genetic testing?

Genetic testing provides information for the individual but also will provide information for the rest of the family. If genetic testing identifies a gene alteration in you we would assume that you had inherited it from either your mother or father. Altered genes can often be passed down through families over generations without being noticed. Therefore, finding a gene alteration in you will have implications for other family members as well. So sharing genetic information in a family is really important. It can provide family members with a real opportunity to protect their health by enrolling in screening programmes to detect cancers as early as possible or even surgical options to help reduce the risk of developing cancer in the first place.

Sometimes people may think if genetic testing does not show anything then there is nothing to tell anyone. However, knowing what is happening in the family can prevent work being repeated as sometimes lots of family members are asking the same questions. It is also very important to remember that, regardless of the results of any genetic testing, the family history itself may mean family members are at a higher risk of cancer anyway and opportunities to protect their health can be offered to them.

• How can I share this information?

On a practical level, you will have this leaflet to share with them and we will also provide a letter after your clinic appointment detailing any other issues discussed.

If a gene alteration is found we will provide you with a ‘relative’s letter’ detailing that a gene alteration has been identified in the family, that they are at risk and how to access testing. We will also guide you as to whom the letter should be passed on to.

On an emotional level, telling family members may be more difficult. You may be worried about upsetting them or have trouble deciding when the right time is. There really is no right or wrong answer to this but it is really useful to think about this before you get your test results and we are more than happy to discuss this with you further. 

• Should I tell my children?

As parents, we want to protect our children from things that we believe can harm them and sometimes this means that we try and ‘hide’ things we think may be difficult for them to cope with. However, we tend to underestimate what children have already picked up on and they are often aware of something going on anyway. They may have noticed letters from the hospital or overheard conversations, they may also pick up cues from adults that they should not ask any questions.

Children in this situation may imagine something really awful is going on, often much worse than the reality, and may even believe it is something bad they have done.

Children value being included and are helped by adults who are honest and direct with communication. It is not always easy but children often cope a lot better than we give them credit for.

Our experience has also shown us that the parents of adult children often do the same. We are happy to talk to you about sharing information with your children during your appointment.

• Who else should I tell?

That is entirely up to you. There is generally no obligation to tell your employer but it might be useful if you anticipate you may need time off work to have screening.                                                     Having friends to discuss this with is helpful for some people but it is important to be aware that people may have differences of opinion that could be in conflict with any decisions you have made.

However, for the majority of people, having discussions with other people is helpful and supportive.

• What happens if I choose to go ahead and have a test?

After you have discussed what genetic testing could mean for you, you may decide to go ahead with testing. We will ask you to sign a consent form and we will take a blood sample from you.                  The laboratory team will then search through the Lynch syndrome genes in your blood sample to see if the code in any of these genes differs from that of a normal gene. The Lynch syndrome genes are large and can take a long time to be looked through. We would expect results to be ready in approximately 3-4 months but please remember sometimes it can be more and sometimes less.

You can discuss with your genetic counsellor or doctor how you wish to receive your results. Some people want their results by letter or over the telephone with the opportunity of a follow-up appointment to discuss any findings, whereas others prefer to come into clinic to have the opportunity to discuss the implications of any findings and next steps. This is entirely up to you and will be discussed during your appointment.

IF, FOR SOME REASON YOU, HAVE NOT RECIEVED YOUR RESULTS WITHIN 3-4 MONTHS AS EXPECTED PLEASE CALL THE LIVERPOOL CENTRE FOR GENOMIC MEDICINE ON 0151 802 5008. Please remember to have your G number and W number handy for this call so we can quickly and correctly identify you.

• What happens if I choose not to go ahead with having a test?

-We will make screening recommendations for your relatives based on the family history of cancer. -We will not be able to offer predictive testing to your relatives.

Attending clinical genetics does not oblige you to go ahead with testing and, if you do go ahead and change your mind about receiving your results, you can do so until you are ready.

Other factors to consider

Insurance and genetics

For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. The types of policy that require a medical history or genetic test are likely to be, life cover, critical illness insurance and income protection insurance.

We would suggest that if yourself or family members are considering taking out new insurance policies in the future that consideration be given to the possible affect genetic test results could have on the ability to gain insurance or the premiums charged. Genetic test results do not affect insurance policies already in place.

The Association of British Insurers (ABI) has a Code of Practice ‘The Concordat and Moratorium on Genetic and Insurance’.

• Insurance companies cannot ask for the Predictive Genetic Test results of individuals or family members (unless for Huntington Disease over £500,000). A Predictive Genetic Test is where an individual has a family member with a genetic condition, but who personally has no symptoms, signs or abnormal medical tests consistent with the condition at time of testing.
• If a family member has been diagnosed with a genetic condition based on a Diagnostic Genetic Test then you or family members will need to mention this when asked to provide your family’s medical history. In many cases Diagnostic Genetic Testing is used to confirm a diagnosis when a particular condition is suspected because of symptoms, signs or abnormal non-genetic tests including unusual findings on a routine blood test or other test.

Sources of further information on insurance and genetics:

The Association of British Insurers Genetics Frequently Asked Questions https://www.abi.org.uk/products-and-issues/topics-and-issues/genetics/genetics-faqs/

Genetic Alliance UK (Charity) Genetics & Insurance http://www.geneticalliance.org.uk/information/living-with-a-genetic-condition/insurance-and-genetic-conditions/

We hope you find this leaflet useful and please do not hesitate to discuss any of the issues identified in this leaflet with the genetics practitioner that is looking after you:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008              Email: lwft.clingen@nhs.net

Useful websites

Genetic Alliance UK www.geneticalliance.org.uk

Cancer research group UK (CRUK) www.cruk.org.uk

National Institute for Health Care and Excellence (NICE) www.nice.org.uk/Guidance/CG41

The leaflet is detailed below, or you can download the 'Predictive Testing for Huntington’s disease' in PDF.

Testing for the Huntington’s Disease gene

This leaflet will explain how our department approaches predictive testing for Huntington’s disease. A predictive test is a test which predicts whether or not a person, who has a family history of Huntington’s disease, but has no symptoms themselves, will actually go on to develop the disease in the future.

The process for predictive testing

The process for predictive testing was developed with the help of the Huntington’s Disease Association (see below for contact details), and is used by genetic centres throughout the United Kingdom.  It involves a series of appointments.

At your appointments you will meet with two members of the clinical team. We make every effort to ensure that you will see the same members of clinical staff at all of your appointments. We welcome and encourage you to bring someone with you for help and support.

What does it involve?

1^st pre-test appointment

No testing is done at this appointment

We need to know about your family history of Huntington’s disease so that, wherever possible, we can ensure that we are testing for the right condition.  It also gives us the chance to explain the signs and symptoms of Huntington’s disease, how it is passed on through families, and what your chances are of having the faulty Huntington’s gene.  We also need to discuss whether doing a test on you could have implications for other members of your family.

We will explain the test to you, how it works, and what the limitations are.  We will discuss the effect a "good news" or "bad news" result may have on you and your family.

If you still wish to be tested, we will arrange a further appointment for you.  Some people, however, decide that they do not wish to go ahead and have the test at this time. You are free to stop at any time during the testing programme, should you want to.

2^nd pre-test appointment

The aim of this appointment is to look at the advantages and disadvantages of knowing for certain whether or not you are going to develop Huntington’s disease. Once we have given you the result you can never go back, so it is important that you are clear that you want to know before we test you.

There will be an agreed time period before the next appointment which gives you time to think and talk through the issues raised. You may also have practical things which will need to be sorted out before your test (such as life insurance). These issues will be discussed in detail at this session.

The test appointment

This appointment gives you the chance to talk through any matters which may have arisen. If you decide you want to have the test done, then we usually offer to take the blood sample.                        It takes 4-6 weeks from the blood sample being taken, for the laboratory to process the test and issue a result.

The result appointment

This appointment is to give you the result of the test in person. We never give out these results over the telephone or in a letter. The date of your result appointment will be agreed with you in advance.

The staff involved in your appointments will not know the result of your test until shortly before you do. We do this so that you can telephone us at any time before the result appointment without worrying that we know something, but are not telling you.

We understand that this process may seem very long, but it is the result of much discussion with people who have already been tested and with staff involved in the testing process.

You do not have to convince us to test you

It is your decision whether or not to have the test. We are here to give you information to help you think through the issues involved, and to give you help and support.

Once again, you can withdraw from the testing process at any time.

For more information:

If you need more advice about any aspect of the predictive testing process for Huntington’s disease, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

Further information and support is available from Huntington’s Disease Association

 

Huntington’s Disease Association

Suite 24, Liverpool Science Park

Innovation centre 1

131 Mount Pleasant

Liverpool

L3 5TF

Telephone 0151 331 5444

Fax 0151 331 5441

Email info@hda.org.uk

Website www.hda.org.uk

 

 

 

The leaflet is detailed below, or you can download the 'Recessive Inheritance' in PDF.

What Are Genes?

Genes are the unique set of instructions inside our bodies which make each of us an individual. There are many thousands of different genes, each carrying a different instruction. If a gene is altered, it can cause a genetic condition or disease. This gene alteration is sometimes known as a mutation.

We have two copies of each gene. One copy is inherited from each of our parents. When we have children, we pass on only one copy of each of our genes.

What Does Recessive Inheritance Mean?

Some conditions are inherited in a recessive way. In recessive conditions, individuals who have only one altered copy of a gene are completely healthy. They are known as carriers, because they carry one altered copy of a gene. Their normal copy of the gene keeps them healthy and compensates for the altered copy of the gene.

Having Children

If both healthy parents carry the same altered recessive gene, then each child they have has a 25% (1 in 4) risk of inheriting the altered gene from both parents and therefore being affected. For each child, regardless of their sex, the risk is the same = 25%.

Children of couples who are both carriers of the same altered recessive gene have a 50% (1 in 2) chance of inheriting one copy of the altered gene from one of their parents. If this happens, they are healthy carriers themselves. There is also a 25% (1 in 4) chance that a child of a carrier couple will inherit two normal copies of the gene. These children will be completely normal.

If only one parent is a carrier of the altered gene, then each of their children has a 50% chance of being a healthy carrier, but will not be affected.

Parents who are closely related to each other, such as first cousins, are more likely to have children with recessive conditions

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

If you need more advice about any aspect of Recessive Inheritance, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

The leaflet is detailed below, or you can download the 'Tissue Studies for Lynch Syndrome' in PDF.

Information for people with a personal or family history of bowel cancer or bowel polyps

Introduction

Lynch syndrome is a hereditary condition that causes people to have an increased risk of developing certain types of cancer.  People with Lynch syndrome have an increased risk of developing colorectal cancer, which is a cancer of the large bowel (colon) and rectum. Women who have Lynch Syndrome also have an increased risk of developing cancer of the womb (uterus) and ovaries.

How common is colorectal, womb and ovarian cancer in the general population?

The estimated lifetime risk of being diagnosed with bowel cancer is 1 in 15 (7%) for males, and 1 in 18 (6%) for females born after 1960 in the UK.¹

The estimated lifetime risk of being diagnosed with uterine cancer is 1 in 36 (3%) for females born after 1960 in the UK.¹ The estimated lifetime risk of being diagnosed with ovarian cancer is 1 in 50 (2%) for females born after 1960 in the UK.¹

How common is Lynch Syndrome

Lynch Syndrome is rare: Approximately 1-3% of people diagnosed with bowel cancer will have Lynch Syndrome.²

Why should I have this test?

Finding out your cancer/bowel polyps are due to Lynch Syndrome will mean we can test other family members to see if they also have Lynch Syndrome. We can then offer screening and/or surgery to you and family members with Lynch Syndrome to detect cancers at a very early stage or even help prevent certain cancers developing in the first place.

What causes Lynch Syndrome?

Lynch Syndrome is caused by an alteration (also called a spelling mistake/error) in one of 4 genes. These genes are called MLH1, MSH2, MSH6 and PMS2.        

What do Tissue Studies involve?

Tissue studies are tests on samples of a cancer or polyp material removed during surgery or bowel screening. These tests may help to identify if the cancers and/or bowel polyps which have occurred in the family are likely to be due Lynch Syndrome. It is important to remember we can only perform tissue testing on certain types of bowel polyps.

What test is performed?

The test we would like to perform is called ImmunoHistoChemistry (IHC) testing.

 IHC testing checks if the 4 genes associated with Lynch Syndrome are working properly. Genes make proteins and IHC tests to see if the MLH1, MSH2, MSH6 and PMS2 proteins are present in your tumor sample or bowel polyp.

What happens if any abnormalities are identified?

If testing shows that one or more of the proteins is missing this could indicate that the tumor/polyp was due to Lynch Syndrome. However, it is important to remember that further testing will be needed to confirm this. You will be offered a follow-up appointment to discuss in more detail should this be the case.

What happens if NO abnormalities are identified?

If the IHC test is normal it is much less likely that bowel cancer and the cancers in the family are due to Lynch Syndrome. In these circumstances screening advice will be offered to family members in relation to the family history of cancer.

What about the results?

The test is complicated and the results can take up to six months.  We will contact the person who has consented to the tests to give them the results.  We will also update our advice about screening and whether any further testing could be useful.  Someone from the genetics team will contact you to discuss this further if appropriate.

What if no tissue is available?

Sometimes we cannot get a tissue sample. However, it may be possible to get one from another relative who has had a related cancer.  If we cannot get tissue from any relatives, we will give advice based on the information we already have. 

What do I need to do?

To go ahead with these tissue studies we need permission from the individual who has had cancer or bowel polyps. If this is not possible because the person with the bowel cancer or bowel polyps has passed away, consent can be obtained from one of the following people: ³

1. Spouse or partner (including civil or same sex partner). The Human Tissue Act states that, for these purposes, a person is another person's partner if the two of them (whether of different sexes or the same sex) live as partners in an enduring family relationship.
2. Parent or child (in this context a child may be of any age and means a biological or adopted child)
3. Brother or sister
4. Grandparent or grandchild
5. Niece or nephew
6. Stepfather or stepmother
7. Half-brother or half-sister
8. Friend of long standing.

 

If you want us to go ahead with these tissue tests, you need to complete and return the appropriate consent form.  If you do not have a consent form and would like one, please contact the department. If you are consenting to tests on tissue of a deceased relative we would encourage you to discuss the decision with other family members.

If you do not want us to go ahead with the tests please let us know so we can provide advice based on the family history you have given without delay.

 

If you need more advice about any aspect of bowel cancer, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

 

Further information

Liverpool Women’s Hospital Lynch Syndrome information leaflet

Cancer Research UK (http://www.cancerresearchuk.org/)

Macmillan (http://www.macmillan.org.uk/Home.aspx)

Human Tissue Authority (HTA) Code of Practice – 1 Consent. Version 14.0 Updated: July 2014 Scheduled review date: July 2016 www.hta.gov.uk.

Consent and confidentiality in clinical genetic practice: Guidance on genetic testing and shearing genetic information A report of the Joint Committee on Medical Genetics  Royal College of Physicians and Royal College of Pathologists 2011.

http://www.Lynch-syndrome-uk.org

https://www.bowelcanceruk.org.uk/

https://www.nhs.uk/conditions/Cancer-of-the-colon-rectum-or-bowel

https://www.genomicseducation.hee.nhs.uk/resources/genetic-conditions-factsheets/item/81-lynch-syndrome

The leaflet is detailed below, or you can download the 'X-Linked Inheritance' in PDF.

What are genes and chromosomes?

Genes are the unique set of instructions inside our bodies which make each of us an individual. There are many thousands of different genes, each carrying a different instruction. If a gene is altered, it can cause a genetic condition or disease. This gene alteration is sometimes known as a mutation.

We have two copies of each gene. One copy is inherited from each of our parents. When we have children, we pass on only one copy of each of our genes. Genes lie on tiny structures called chromosomes. Females have two X chromosomes and males have one X and one Y chromosome. The Y chromosome is much smaller than the X chromosome and contains fewer genes.

What does X-linked inheritance mean?

X-linked conditions occur when an altered gene is located on the X chromosome.

If a female has an altered gene on one of her two X chromosomes, then she will be a healthy carrier. She is healthy because she has a second normal copy of the gene on her other X chromosome.

If a male has an altered gene on his X chromosome, then he will be affected as he has only one X chromosome.

Having children

Carrier Females - If a female carrier has a boy, there is a 50% (1 in 2) risk that the boy will be affected by a condition caused by the altered gene that she carries on her X chromosome.

If a female carrier has a girl, there is a 50% (1 in 2) risk that the girl will inherit the X chromosome altered gene, If this happens she will most likely be a healthy carrier, like her mother.

Affected Males (diagram B) - When males who are affected by X-linked conditions have children, all of their daughters inherit the altered gene on their X chromosome. These daughters will all be carriers.

Men do not pass on their X chromosomes to their sons. Therefore, all the sons of men with X-linked conditions are completely unaffected (diagram B).

Note - Sometimes boys are born with X-linked conditions even though their mothers are not carriers. When this happens, it is particularly important to get specialist advice about future pregnancies.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

If you need more advice about any aspect of X-linked Inheritance, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

 

The leaflet is detailed below, or you can download the 'Microarray Leaflet for Parents' in PDF.

Introduction

The doctor looking after you, or your child, has decided to request a test called a microarray. This leaflet aims to explain what this test involves and the possible outcomes.

What are chromosomes and genes? 

Each person has about 20,000 pairs of genes.  They work like instructions that determine things such as the colour of our eyes, how many fingers and toes we have and how tall or short we are.  Genes are so small that they cannot be seen, even under a powerful microscope.  They are arranged along strands, rather like beads along a string. These strands are called chromosomes, and are inside most of the cells in our body. 

Most cells in a person's body contain 23 pairs of chromosomes (46 in total), which can be seen down the microscope.  To help tell which chromosome is which, each pair has been given a number.  Pair number 1 is the largest; pair number 2 is the next largest and so on right down to pair number 22 which is the smallest.  The remaining two chromosomes (X and Y) are called the sex chromosomes and they determine whether a person is male (XY) or female (XX).

Everyone has some small variations on their chromosomes, but not all of these cause problems.  However, some people who have certain changes in the number or structure of their chromosomes may have a variety of problems, including developmental delay, learning and behavioural problems, heart defects, abnormalities of the fingers or toes and many others. Importantly, everyone has some small changes on their chromosomes, not all of them cause problems. 

Chromosome tests 

Karyotype – Chromosomes cannot be seen by the naked eye but can be seen under powerful microscopes.  A “normal” result means that there are no obvious large pieces of chromosome material missing or extra and the chromosomes are arranged in the right order. 

Microarray – This test uses techniques to look at the chromosomes in much finer detail, and can pick much smaller pieces of missing (deletion) or extra (duplication) chromosome than can be seen down a microscope.

What happens now?

A blood sample will be needed from your child and sent to our laboratory for microarray.  Results will take approximately 12 weeks and the doctor will contact you once the results are received. 

If the laboratory has a sample of DNA stored from a previous genetic test that your child has had, it may be possible to test this DNA sample.  However a new blood sample may be required.

Results

There are three possible outcomes from the microarray.

1. The chromosomes may appear entirely normal. A normal microarray test does not rule out all genetic conditions as there may still be changes in individual genes, which cannot be detected by a microarray test.
2. The test may reveal a change which is highly likely to account for the problems that your child has. If we identify such a change then we can see you in clinic again to discuss this.
3. We could identify a change that we do not know the significance of – in other words, we do not know if it may be the cause of your child’s problems or not. In this case, we may ask for samples from both parents to see whether either of you have the same change as your child has in their DNA.  This may help us to interpret the meaning of the genetic change, but some changes will remain uncertain.

There is also a very small chance that we could pick up something unrelated to your child’s current problems which may have implications for their/the family’s future health e.g. early onset cancer or heart disease.  We would inform you of this result.

If you need more advice about any aspect of Microarray, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

 

The leaflet is detailed below, or you can download the 'PALB2 gene alteration identified' in PDF

Why have I been given this information sheet?

You have been given this information sheet because you, or someone in your family, has been found to have an alteration in a gene called PALB2. This sheet should accompany a letter from our Genetics Service which will have additional information and recommendations specific for your family.

What is PALB2?

PALB2 is a gene that is known to be connected with breast cancer risk.

What cancer risks are there if you have a PALB2 gene alteration?

The table below outlines the cancer risks associated with having PALB2 gene alteration.

If you have had breast cancer, the PALB2 gene alteration is likely to be the main explanation for this. There may also have been other factors, both genetic and environmental, as well as an element of chance.   

What cancer surveillance is available for individuals with a PALB2 alteration?

Women who have a PALB2 gene alteration are offered high risk breast screening. This involves:

• Annual magnetic resonance imaging (MRI) scan from 25-39 years
• Annual MRI AND mammography from 40-50 years
• Annual mammography from 51-71 years (some women may continue to receive MRI too)

For women who have a 50% chance of inheriting a PALB2 gene alteration but do not want a genetic test, their level of breast screening is worked out based on their personal family history.

Most NHS routine or high risk breast screening stops after the age of 70 or in some places 73.  You can still have screening after this, and can arrange an appointment by contacting your local breast screening unit.  This is something we would recommend if you were a carrier of a gene alteration. We also suggest that women carry out monthly self-examination of the breasts.

The aim of breast surveillance is to detect breast cancers at an earlier stage, when the cancer has a better prognosis and is easier to treat. However, surveillance is not perfect and may miss cancers. In addition, sometimes changes are seen on the scans that later turns out not to be a cancer, but do cause worry and can lead to unnecessary extra tests. We are not currently recommending surveillance for other cancers.

What preventative surgery options are available for individuals with a PALB2 alterations?

We know that your risk of cancer will vary according to your family history. If you have a strong family history of breast cancer you may wish to consider preventative surgery of the breasts (also called risk reducing mastectomy). If you have a close relative affected with ovarian cancer then preventative removal of the ovaries may also be an option to consider. Please talk to your Genetic Counsellor or Clinical Geneticist if you would like to look into this further.

How is the PALB2 gene alteration inherited?

We have two copies of every gene including PALB2. We give one copy of each gene to our children in the sperm and one copy in the egg. Someone with a PALB2 gene alteration usually has this alteration in only one copy of PALB2. They also have a normal copy of the PALB2 gene. Their children can inherit either the normal or the altered copy. This means they have a 50% (1 in 2) chance of having the same gene alteration.

Who should be offered a test for the PALB2 gene alteration?

Genetic testing for the PALB2 alteration may be helpful for your relatives. Genetic testing is only offered through a Genetic Service. Your Genetic Counsellor or Clinical Geneticist can provide a letter for your relative to take to their GP to request a referral to Genetics.

What can I do to help my risk if I have a PALB2 gene alteration?

We recommend all women minimise risk of breast cancer by maintaining a healthy diet and taking plenty of exercise. You should also report any changes in your breasts to your GP. If you have a personal or family history of breast cancer you should discuss this with your GP before taking hormone replacement therapy.

Where can I get further information?  

The PALB2 website www.PALB2.org is run by the PALB2 Interest Group and provides further information to families and health professionals.

Are there any research studies for PALB2?  

If you would like to know more about research please contact the PALB2 Interest group through their website www.PALB2.org.

 

If you need more advice about any aspect of PALB2 genetic testing, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008              Email: lwft.clingen@nhs.net

 

                                                                              

 

The leaflet is detailed below, or you can download the 'Microarray Leaflet for Adults' in PDF

Introduction

Your doctor has decided to request a test called a microarray. This leaflet aims to explain what this test involves and the possible outcomes.

What are chromosomes and genes? 

Each person has about 20,000 pairs of genes.  They work like instructions that determine things such as the colour of our eyes, how many fingers and toes we have and how tall or short we are.  Genes are so small that they cannot be seen, even under a powerful microscope.  They are arranged along strands, rather like beads along a string. These strands are called chromosomes, and are inside most of the cells in our body. 

Most cells in a person's body contain 23 pairs of chromosomes (46 in total), which can be seen down the microscope.  To help tell which chromosome is which, each pair has been given a number.  Pair number 1 is the largest; pair number 2 is the next largest and so on right down to pair number 22 which is the smallest.  The remaining two chromosomes (X and Y) are called the sex chromosomes and they determine whether a person is male (XY) or female (XX).

Everyone has some small variations on their chromosomes, but not all of these cause problems.  However, some people who have certain changes in the number or structure of their chromosomes may have a variety of problems, including developmental delay, learning and behavioural problems, heart defects, abnormalities of the fingers or toes and many others.

Chromosome tests 

Karyotype – Chromosomes cannot be seen by the naked eye but can be seen under powerful microscopes.  A “normal” result means that there are no obvious large pieces of chromosome material missing or extra and the chromosomes are arranged in the right order. 

Microarray – This test uses techniques to look at the chromosomes in much finer detail, and can pick much smaller pieces of missing or extra chromosome than can be seen down a microscope. Missing sections of chromosomes are sometimes called deletions, and extra sections are called duplications.

What happens now?

A blood sample will be needed from you and sent to our laboratory for microarray.  Results will take approximately 12 weeks and the doctor will contact you once the results are received. 

If the laboratory has a sample of DNA stored from a previous genetic test that you have had, it may be possible to test this DNA sample.  However a new blood sample may be required.

Results

There are three possible outcomes from the microarray.

1. The chromosomes may appear entirely normal. A normal microarray test does not rule out all genetic conditions as there may still be changes in individual genes, which cannot be detected by a microarray test.
2. The test may reveal a change which is highly likely to account for the problems that you have. If we identify such a change then we can see you in clinic again to discuss this.
3. We could identify a change that we do not know the significance of – in other words, we do not know if it may be the cause of your problems or not. In this case, we may ask for samples from your parents to see whether either of them have the same change as you in their DNA.  This may help us to interpret the meaning of the genetic change, but some changes will remain uncertain.

There is also a very small chance that we could pick up something unrelated to your current problems which may have implications for your/the family’s future health e.g. early onset cancer or heart disease. We would inform you of this result.

If you need more advice about any aspect of Microarray, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

The leaflet is detailed below, or you can download the 'ATM Gene alteration identified' in PDF

Why have I been given this information sheet?

You have been given this information sheet because you, or someone in your family has been found to have an alteration in a gene called ATM. This sheet should accompany a letter from our Clinical Genomics Service which will have additional information and recommendations specific for your family.

What is ATM?

ATM is a gene that is known to be connected with breast cancer risk.

What cancer risks are there if you have an ATM gene alteration?

We estimate that someone who has an ATM gene alteration has approximately a 17-30% chance of developing breast cancer over their lifetime, falling into the moderate risk group. An exception to this is a specific ATM alteration, c.7271T>G, which confers a risk of breast cancer over 30% which is characterised as high risk.¹ These risks are compared to the general population risk of around 15% (1 in 7) which is considered a low risk of developing breast cancer. It is possible that ATM alterations also increase the risks of developing other types of cancer and these risks should hopefully become clearer in the future. 

If you have had breast cancer, the ATM gene alteration is likely to be the main explanation for this. However, there may also have been other factors involved, both genetic and environmental, as well as an element of chance.

How is the ATM gene alteration inherited?

We have two copies of every gene including ATM. We give one copy of each gene to our children in the sperm and one copy in the egg. Someone with an ATM gene alteration usually has this alteration in only one copy of ATM. They also have a normal copy of the ATM gene. Their children can inherit either the normal or the altered copy. This means they have a 50% (1 in 2) chance of having the same gene alteration.

If someone with an ATM alteration has a partner who also carries an alteration in one of their ATM genes then there is a 25% (1 in 4) chance of both parents passing on an ATM alteration which leads to a rare condition known as ataxia telangiectasia. This is a rare condition that causes enlarged blood vessels under the skin and uncoordinated movements among other neurological symptoms. However, the chance of someone in the general population carrying an ATM alteration is low. 

What cancer surveillance is available for individuals with an ATM alteration?

We recommend increased surveillance using mammograms from the age of 40 years. For those individuals why carry the high risk ATM alteration we recommend using a combination of breast MRI and mammograms from the age of 30 years. The aim is to detect breast cancers at an earlier stage, when the cancer has a better prognosis and is easier to treat. However, surveillance is not perfect and may miss cancers. In addition, sometimes changes are seen on the scans that later turns out not to be a cancer, but do cause worry and can lead to unnecessary extra tests. We are not currently recommending surveillance for other cancers.

What preventative surgery options are available for individuals with an ATM alteration?

At the moment we do not have enough long-term data on the breast cancer risks in ATM mutation carriers to know whether preventative removal of the breasts (also called risk reducing mastectomy) should be considered. Please talk to your Genetic Counsellor or Clinical Geneticist if you would like to look into this further.

Who should be offered a test for the ATM gene alteration?

Genetic testing for the ATM alteration may be helpful for your relatives. Genetic testing is only offered through a Clinical Genomics Service. Your Genetic Counsellor or Clinical Geneticist can provide a letter for your relative to take to their GP to request a referral to Clinical Genomics.

What can I do to help my risk if I have an ATM gene alteration?

We recommend all women minimise risk of breast cancer by maintaining a healthy diet and having plenty of exercise. You should also report any changes in your breasts to your GP. If you have a personal or family history of breast cancer you should discuss this with your GP before taking hormone replacement therapy.

Where can I get further information?

The AT society (ataxia telangiectasia) is a registered charity that support people who have two ATM alterations resulting in ataxia telangiectasia. Their website provides information and resources for people with this condition. Within the genetic aspects of A-T section on their website you can also find information about being a carrier of one ATM alteration.

Are there any research studies for ATM?

There are many new and exciting research studies looking at the impact of genomics on cancer development. One such study is the Epidemiological Study Of Familial Breast Cancer (Embrace) which aims to identify risk factors contributing to the development of cancer in those with an inherited cancer gene alteration. If you are interested in discussing the possibility of participating in any research studies please get in contact with the Clinical Genomics team at Liverpool Women’s Hospital.   

If you need more advice about any aspect of ATM, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008              Email: lwft.clingen@nhs.net

 

The leaflet is detailed below, or you can download the 'Predictive testing for a Breast Cancer 1(BRCA2) Gene alteration' leaflet in PDF.

 

Cancer is common in the general population with 1 in 2* people being diagnosed with a cancer in their lifetime. Approximately 1 in 7* women will be diagnosed with breast cancer and most cancer occurs just by chance. Our suspicions of an inherited explanation for the cancers in a family are raised if the same or related cancers occur in several family members on the same side of the family, usually across different generations and at a younger age than expected. This is why genetic testing would be offered to a family.

 *Cancer Research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960.

What are genes and chromosomes? 

Humans are made up of trillions of cells. At the centre of almost all of your cells is a ball-shaped structure called the nucleus, inside of which are 46 thread-like structures called chromosomes. Chromosomes are long strands of DNA (DeoxyriboNucleic Acid). It is estimated that if a strand of DNA was stretched out, it would be around two meters long, even though the average cell is smaller than a pinhead.

 

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

Image Source: https://cpmc.coriell.org

We have 23 pairs of chromosomes; one of each pair is inherited from your mother and one of each pair from your father. Chromosomes 1-22 are arranged in size order with number 1 being the largest and 22 the smallest. The 23rd pair of chromosomes determines a person’s sex. Most males are XY and most females are XX. Chromosomes contain an estimated 20-30,000 pairs of genes that make us who we are. As we have pairs of chromosomes we therefore have pairs of genes.

Genes are often called the blueprint for life because they tell each of your cells what to do and when to do it. For example, some genes determine how tall you will be; some what colour your hair will be; some genes are responsible for maintenance in our bodies and some for our development, and so on. Genes do this by making proteins. In fact, each gene is really just a ‘recipe’ or a code for making a certain protein. In order for a gene to do the job it is supposed to do, the ‘recipe’ or code needs to be written correctly. If the ‘recipe’ is wrong, the protein is either not made, or is made incorrectly so cannot do the job it is supposed to do.  This is sometimes called a gene alteration, a spelling mistake or a gene mutation.

 

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

What is the role of the BRCA2 gene?

The role of the BRCA2 gene is to protect the body against developing cancer in certain areas of the body. BRCA2 genes are called tumour suppressor genes and the protein produced from them helps prevent cells from growing and dividing too rapidly or in an uncontrolled way. The pair of BRCA2 genes are found on chromosome 13. 

What are the main cancer risks associated with having an altered BRCA2 gene?

 

There may also be a small risk of developing other cancers including pancreatic** and skin cancer (particularly melanoma) but not enough to warrant routine additional screening. However, it would be important to have a low threshold for seeking medical help for any concerning or persistent symptoms.
 
**In families with a BRCA2 gene alteration and a history of pancreatic cancer, pancreatic screening is offered to family members found to have a BRCA2 gene alteration.

What can be done to help manage these risks?

For each of the high risk cancers, screening and surgical options are discussed.  Different options are available to men and women, and options can also differ dependent on what age you are. 

Breast screening

Women who have a BRCA2 gene alteration are offered high risk breast screening.

 This involves:

• Annual magnetic resonance imaging (MRI) scan from 25-39 years
• Annual MRI AND mammography from 40-50 years
• Annual mammography from 51-71 years (some women may continue to receive MRI too)

Women who have a 50% chance of inheriting a BRCA2 gene alteration but choose not to have a genetic test will be offered the screening described above until the age of 50. These women will then need to have genetic testing in order to continue to receive high risk breast screening, otherwise they will join the NHS Breast Screening Programme for a mammogram every three years.

Most NHS routine or high risk breast screening stops after the age of 70 or in some places 73.  You can still have screening after this, and can arrange an appointment by contacting your local breast screening unit.  This is something we would recommend if you were a carrier of a BRCA2 gene alteration. We also suggest that women carry out monthly self-examination of the breasts.

Men are not offered any breast screening, but we suggest they check their chest and armpit areas and seek medical advice for any unusual lumps.

 Breast surgery

Women who have a BRCA2 gene alteration also have the option of having surgical removal of both breasts (bilateral mastectomy). Although this procedure could significantly reduce the risk of developing breast cancer it will not remove the risk entirely. We also recognize this is a radical step that requires careful consideration. Therefore, women who choose this option are fully supported throughout the process and not rushed into making any decisions.

 Ovarian screening and surgery

Ovarian screening involves regular blood tests approximately 3-4 times a year, to measure a marker in the blood called CA125 and also by annual ultrasound from the age of 35. However, ovarian screening does not reliably inform us of cancers early enough in order for them to be treated effectively. 

Therefore, for women who are BRCA2 carriers, over the age of 35/40 and have completed their families we would encourage them to think about having their ovaries and fallopian tubes removed (bilateral salpingo-oophorectomy).  This can significantly decrease the risk of developing ovarian cancer but, again, the risk of cancer is never removed entirely. This may also have some impact on reducing the risk of breast cancer.  

There are clear advantages to having your ovaries and fallopian tubes removed, however they do need to be weighed with the potential disadvantage of being put into an early menopause and the possible need for hormone replacement therapy (HRT).  The advantages and disadvantages of HRT could be further discussed with a gynecologist if you choose to go ahead with this process.

Chemoprevention

Recent guidelines have suggested that ladies at high risk of breast cancer be offered chemoprevention medications. Research suggests these medications can reduce the risk of developing breast cancer however they do have significant side effects. Please ask for a leaflet outlining the risks and benefits of chemoprevention if you think this is something you might be interested in. 

Prostate screening for people with a BRCA2 gene alteration

Prostate screening should be undertaken annually from the age of 40 in people who have a BRCA2 gene alteration. This can be provided through the GP.

How are BRCA2 gene alterations passed down (inherited) through families?

The way BRCA2 gene alterations are inherited is called DOMINANT inheritance. This is caused by an alteration in only one copy of the BRCA2 gene. Even though we each have 2 copies of the BRCA2 gene the normal copy cannot compensate for the altered copy and a person with one altered BRCA2 gene has an increased risk of developing cancer.

If a parent carries an altered BRCA2 gene, each of their children has a 50%, or 1 in 2 chance of inheriting the altered gene and therefore having an increased risk of developing cancer. For each child, regardless of their sex, the risk is the same = 50%.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

What is predictive testing?

Predictive testing is offered to family members who are known to be at risk of inheriting a gene alteration that has been identified in the family but are currently well. Predictive testing is usually offered over a series of appointments to allow the opportunity to consider options and choices with time for reflection in-between. How many appointments a person requires varies considerably from person to person and is negotiated on an individual basis with your genetic counsellor team. The overall aim of the predictive testing process is to help prepare you for your results whatever they are.

• What are the issues to think about when deciding whether or not to have a gene test?

A genetic test can establish whether you have an alteration in a gene which could affect your health.
It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations. Many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.

There are reasons for and against having a genetic test. Within one family, relatives often have different views. You should try to make your own decision, without feeling pressured from relatives or other influences.

You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor.

• How do you think you would cope if the test were to show that you have inherited the altered gene?

For some people, knowing that they have the altered gene is preferable to living with uncertainty. Having a genetic test enables them to make decisions about the future and about screening and measures to reduce their risk. Other people may prefer not to have the test because they may feel very anxious if the test shows that they have the altered gene.

•  How do you think you would cope if the test were to show that you have not inherited the altered gene?

Perhaps surprisingly, it can often take people some time to get used to the knowledge that they do not have the altered gene. This can be particularly difficult when other relatives have a different result.

People who do not have the altered gene have the same chance of developing cancer as other people in the general population.

•  If the test were to show that you have the altered gene, this would mean that your children would also be at risk of having the altered gene. How do you think you might feel about this?

Having a genetic test may be important to other people, such as your children. It will help them to understand their own risk and if necessary make choices about screening and risk reducing options.

It can be very difficult knowing that you could have passed on an altered gene to your children. This can be hard to deal with even if you know that you had no control over which genes you passed on.

•  If you were to have the test, would you want to tell anyone the test results?

 It is important to think about who you would want to know about your test as it is very personal information. Many people who attend our clinic find that it helps to confide in a partner, trusted friend or relative.

•  Would having the test affect your ability to get life or medical insurance?

At present, if you have already obtained your insurance, having the test should not affect your current policies. However, it is not possible to know whether it will affect your ability to get or to change insurance policies in the future.

•  Would having the test affect your employment?

If the test shows you have the altered gene it would be your decision whether or not to inform your present employers. Some employers might ask about this if you apply for a new job.

It is important that each family member makes the decision that is best for them. We will support you whether you decide to have the test or whether you decide against having the test. It is your decision!

•  What happens if I choose to go ahead and have a test?

 - After you have the opportunity to discuss the positives and negatives of predictive testing, if you wish to have the test you will be asked to read and sign a consent form and a small blood sample will then be taken.

- Once the blood is taken, the laboratory staff would test the sample to find out whether or not you have inherited the altered gene known in your family.

-Test results are usually available 4-6 weeks after having your blood taken and you can choose to have your results over the phone or in a clinic appointment.

 IF, FOR SOME REASON YOU, HAVE NOT RECIEVED YOUR RESULTS WITHIN 4-6 WEEKS AS EXPECTED PLEASE CALL THE LIVERPOOL CENTRE FOR GENOMIC MEDICINE ON 0151 802 5008. Please remember to have your G number and W number handy for this call so we can quickly and correctly identify you.

•  What happens if I choose not to go ahead with having a test?

We may still recommend screening to you as explained earlier in this leaflet.

You can change your mind and decide not to have the test at any time before the result is given.

Other factors to consider

Insurance and Genetics

For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. The types of policy that require a medical history or genetic test are likely to be, life cover, critical illness insurance and income protection insurance.

We would suggest that if yourself or family members are considering taking out new insurance policies in the future that consideration be given to the possible affect genetic test results could have on the ability to gain insurance or the premiums charged. Genetic Test results do not affect insurance policies already in place.

The Association of British Insurers (ABI) has a Code of Practice ‘The Concordat and Moratorium on Genetic and Insurance’.

• Insurance companies cannot ask for the Predictive Genetic Test results of individuals or family members (unless for Huntington Disease over £500,000). A Predictive Genetic Test is where an individual has a family member with a genetic condition, but who personally has no symptoms, signs or abnormal medical tests consistent with the condition at time of testing.

• If a family member has been diagnosed with a genetic condition based on a Diagnostic Genetic Test then you or family members will need to mention this when asked to provide your family’s medical history. In many cases Diagnostic Genetic Testing is used to confirm a diagnosis when a particular condition is suspected because of symptoms, signs or abnormal non-genetic tests including unusual findings on a routine blood test or other test.

Sources of further information on Insurance and Genetics:

The Association of British Insurers Genetics Frequently Asked Questions

https://www.abi.org.uk/products-and-issues/topics-and-issues/genetics/genetics-faqs/

Genetic Alliance UK (Charity) Genetics & Insurance

http://www.geneticalliance.org.uk/information/living-with-a-genetic-condition/insurance-and-genetic-conditions/

Family planning

Everyone who has an inherited genetic condition can choose from a variety of options to ensure they do not pass it on. It is a highly personal decision and there is certainly no expectation that couples have to do anything to prevent passing on a BRCA1 gene alteration, but for couples who wish to consider this, some of the choices can include:

•  Preimplantation genetic diagnosis (PGD)

PGD involves the use of assisted reproductive technology (ART)|, which is also offered to couples with fertility problems. The aim is to obtain and fertilize a number of eggs. Once fertilized, the embryos develop for six days and then a number of cells are removed from each embryo. The genetic material (DNA or chromosomes) within each cell is then tested for the genetic or chromosome abnormality. Up to two unaffected embryos are then transferred to the uterus with the hope that they will implant and form a pregnancy. If successful, the baby should not be affected by the disorder it was tested for.

More information can be obtained here: http://www.pgd.org.uk.

•  Adoption
•  Sperm or egg donation: dependent on who carries the gene alteration.

Our experience is however that very few couples who carry a BRCA2 gene alteration choose any of the above options.

Oral Contraceptives

There have been a number of studies looking at the relationship between taking oral contraceptives and breast cancer risk but unfortunately the findings can often differ between different studies. However, overall, we know that taking the combined oral contraceptive pill (COC) increases the risk of breast cancer in all women. The risk appears to be confined to current and recent use and the risk drops once you stop taking the pill, and will return to normal after a number of years without use. It is felt that 10 years after stopping the COC, the breast cancer risk is the same as if you had never taken it at all.

For women with a BRCA2 gene alteration, taking the combined oral contraceptive pill (COC) is not thought to be associated with an increased risk of breast cancer above that of the BRCA2 associated cancer risks discussed above.

Use of COC also reduces the risk of ovarian cancer proportionally to the duration of use but should never be prescribed for this reason only.

There is no evidence regarding progesterone only contraceptives and breast cancer risk associated with family history.

You should discuss the use of oral contraceptives with your GP to weigh up the risks and benefits to help you make the decision that is right for you. You may also want to look at the Cancer Research UK website for further information.

 

Useful websites

Genetic Alliance UK                                                               www.geneticalliance.org.uk

 Cancer research group UK (CRUK)                                     

www.cruk.org.uk

National Institute for Health Care and Excellence (NICE)    

www.nice.org.uk/Guidance/CG41

If you need more advice about any aspect of BRCA2 predictive testing, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown Street

Liverpool

L8 7SS

Telephone: 0151 802 5001 or 5008              Email: lwft.clingen@nhs.net

 

 

 

 

The leaflet is detailed below, or you can download the 'Predictive Genetic testing for Lynch Syndrome' leaflet in PDF

Cancer is common in the general population with 1 in 2* people being diagnosed with a cancer in their lifetime and most cancer occurs just by chance. Our suspicions of an inherited explanation for the cancers in a family are raised if the same or similar cancers occur in several family members on the same side of the family, usually across different generations and at a younger age than expected. This is why genetic testing would be offered to a family.

*Cancer research UK (2015) estimated lifetime risk of being diagnosed, people born after 1960

What are genes and chromosomes?

Humans are made up of trillions of cells. At the centre of almost all of your cells is a ball-shaped structure called the nucleus, inside of which are 46 thread-like structures called chromosomes. Chromosomes are long strands of DNA (DeoxyriboNucleic Acid). It is estimated that if a strand of DNA was stretched out, it would be around two meters long, even though the average cell is smaller than a pinhead.

 

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

 

Image Source: https://cpmc.coriell.org

We have 23 pairs of chromosomes; one of each pair is inherited from your mother and one of each pair from your father. Chromosomes 1-22 are arranged in size order with number 1 being the largest and 22 the smallest. The 23rd pair of chromosomes determines a person’s sex. Most males are XY and most females are XX. Chromosomes contain an estimated 20-30,000 pairs of genes that make us who we are. As we have pairs of chromosomes we therefore have pairs of genes.

Genes are often called the blueprint for life because they tell each of your cells what to do and when to do it. For example, some genes determine how tall you will be; some what colour your hair will be; some genes are responsible for maintenance in our bodies and some for our development, and so on. Genes do this by making proteins. In fact, a gene may act by being a ‘recipe’ or a code for making a certain protein. In order for a gene to do the job it is supposed to do, the ‘recipe’ or code needs to be written correctly. If the ‘recipe’ is wrong, the protein is either not made, or is made incorrectly so cannot do the job it is supposed to do. This is sometimes called a gene alteration, a spelling mistake or a gene mutation.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

What is Lynch syndrome?

Lynch syndrome is a hereditary condition that causes people to have an increased risk of developing certain types of cancer and is caused by a gene alteration. Lynch syndrome also used to be known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC).

What genes are associated with Lynch syndrome?

There are currently 4 genes that we know of that, if they are altered, can be associated with the development of Lynch syndrome. These genes are known as MLH1, MSH2, MSH6 and PMS2. In fact we all have 2 copies each of these genes and they have a very important role to protect certain parts of our body from developing cancer. These genes are called mis-match repair genes and help protect us from developing cancer by detecting and correcting errors that can occur in DNA when cells copy themselves (DNA replication errors). They are like a quality control system that will either repair the mistakes in the DNA or gets rid of the cell with the mistake to stop it being copied anymore. If there is an alteration in one of our Lynch syndrome genes this quality control system is less effective and the person then has an increased susceptibility to developing cancer. But having an alteration in a Lynch Syndrome gene does not mean a person will definitely go on to develop cancer.

What are the main cancer risks associated with having a Lynch syndrome gene alteration?

 

There may also be a small risk of developing other cancers including kidney (renal) cancer and pancreatic cancer but not enough to warrant routine screening. However, screening for these cancers may be offered if family members have developed these cancers. There is also a low risk of other cancers for which screening is not offered however, it would be important to have a low threshold for seeking medical help for any concerning or persistent symptoms.

What can be done to help manage these risks?

For each of the high risk cancers, screening and surgical options are discussed. Different options are available to men and women, and options can also differ dependent on what age you are.

Screening for people with Lynch syndrome

What does bowel screening involve?

This is an internal examination of the large bowel, also known as colonoscopy. The purpose of a colonoscopy is to look for cancer and polyps.
Polyps are quite common in the general population, but they are very common in people with Lynch syndrome. Most polyps are harmless and will not cause any trouble. However, the occasional polyp may grow over many years and develop into a cancer, as illustrated:

Image source: NHS National Genetics and Genomics Education Centre

It may be possible to prevent a cancer from forming by removing polyps. Removal of polyps is usually carried out during a colonoscopy.

How is Helicobacter pylori screened for?

People with Lynch syndrome should also be tested for the presence of a bacterium called Helicobacter pylori (H.pylori) and this can be done through your GP. H.pylori can live in the gut and can lead to chronic gastritis which in turn could lead to an increased risk of stomach cancer for people who carry a Lynch syndrome gene alteration. H.pylori can be detected by a breath test, blood test or stool sample and if found, eradicated with a course of antibiotics.

Why should I discuss aspirin use with my GP?

Aspirin taken daily for 2 years or more could reduce the risk of colorectal cancer in people with Lynch syndrome (LS), says National Institute for Clinical Excellence, NICE guidance 151. Aspirin is not licensed for this purpose so if it is prescribed for cancer risk reduction this is called an ‘off-label’ use of aspirin.
The best dose of aspirin is not yet clear but the UK Cancer Genetics Group recommend those between 25 and 65 years consider taking 150mg if 70kg or under and 300mg for people who weigh more than 70kg. These recommendations are likely to be updated over the coming years as more evidence becomes available.

PLEASE REMEMBER; Aspirin is a drug that can have serious side effects. It should never be taken without first being reviewed by your GP to make sure there is no reason you should not take it. We are not recommending consideration of aspirin usage to anyone without Lynch syndrome.

Can I have screening for ovarian and endometrial cancer rather than surgery?

Screening for ovarian cancer involves regular blood tests approximately 3-4 times a year, to measure a marker in the blood called CA125 and also by annual ultrasound scan from the age of 35.
Screening for endometrial screening involves an annual transvaginal ultrasound scan and endometrial sampling (sampling of the lining of the womb).
However, ovarian and endometrial screening does not always reliably inform us of cancers early enough in order for them to be treated effectively. Therefore for women with Lynch syndrome, we encourage them to consider surgery to help manage their risk of gynecological cancers as detailed above.

What else can I do to help protect my health?

We suggest that individuals at increased familial risk of colorectal cancer should be strongly encouraged not to smoke, to maintain a normal BMI, to moderate their consumption of red and processed meat, and to exercise regularly.

How are Lynch syndrome gene alterations passed down (inherited) through families?

The way Lynch Syndrome gene alterations are inherited is called DOMINANT inheritance. This is caused by an alteration in only one copy of a Lynch syndrome gene. Even though we each have 2 copies of Lynch syndrome genes a normal copy cannot compensate for an altered copy and a person with one altered Lynch syndrome gene has an increased risk of developing cancer.
If a parent carries an altered Lynch Syndrome gene, each of their children has a 50%, or 1 in 2 chance of having inherited the altered gene and therefore having an increased risk of developing cancer. For each child, regardless of their sex the risk is the same = 50:50.

Image source: https://www.genomicseducation.hee.nhs.uk/image-library/

What is predictive testing?

Predictive testing is offered to family members who are known to be at risk of inheriting a gene alteration that has been identified in the family but are currently well. Predictive testing is usually offered over a series of appointments to allow the opportunity to consider options and choices with time for reflection in-between. How many appointments a person requires varies considerably from person to person and is negotiated on an individual basis with your genetic counsellor team. The overall aim of the predictive testing process is to help prepare you for your results whatever they are.

• What are the issues to think about when deciding whether or not to have a gene test?

A genetic test can establish whether you have an alteration in a gene which could affect your health. It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations. Many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.
There are reasons for and against having a genetic test. Within one family, relatives often have different views. You should try to make your own decision, without feeling pressured from relatives or other influences. You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor.

• How do you think you would cope if the test were to show that you have inherited the altered gene?

For some people, knowing that they have the altered gene is preferable to living with uncertainty. Having a genetic test enables them to make decisions about the future and about screening and
measures to reduce their risk. Other people may prefer not to have the test because they may feel very anxious if the test shows that they have the altered gene.

• How do you think you would cope if the test were to show that you have not inherited the altered gene?

Perhaps surprisingly, it can often take people some time to get used to the knowledge that they do not have the altered gene. This can be particularly difficult when other relatives have a different result.
People who do not have the altered gene have the same chance of developing cancer as other people in the general population.

• If the test were to show that you have the altered gene, this would mean that your children would also be at risk of having the altered gene. How do you think you might feel about this?

Having a genetic test may be important to other people, such as your children. It will help them to understand their own risk and if necessary make choices about screening and risk reducing options.
It can be very difficult knowing that you could have passed on an altered gene to your children. This can be hard to deal with even if you know that you had no control over which genes you passed on.

• If you were to have the test, would you want to tell anyone the test results?

It is important to think about who you would want to know about your test as it is very personal information. Many people who attend our clinic find that it helps to confide in a partner, trusted friend or relative.

• Would having the test affect your ability to get life or medical insurance?

At present, if you have already obtained your insurance, having the test should not affect your current policies. However, it is not possible to know whether it will affect your ability to get or to change insurance policies in the future.

• Would having the test affect your employment?

If the test shows you have the altered gene it would be your decision whether or not to inform your present employers. Some employers might ask about this if you apply for a new job.
It is important that each family member makes the decision that is best for them. We will support you whether you decide to have the test or whether you decide against having the test. It is your decision!

• What happens if I choose to go ahead and have a test?

After you have the opportunity to discuss the positives and negatives of predictive testing, if you wish to have the test you will be asked to read and sign a consent form and a small blood sample will then be taken.

Once the blood is taken, the laboratory staff would test the sample to find out whether or not you have inherited the altered gene known in your family.
Test results are usually available 4-6 weeks after having your blood taken and you can choose to have your results over the phone or in a clinic appointment.

IF, FOR SOME REASON YOU, HAVE NOT RECIEVED YOUR RESULTS WITHIN 4-6 WEEKS AS EXPECTED PLEASE CALL THE LIVERPOOL CENTRE FOR GENOMIC MEDICINE ON 0151 802 5008. Please remember to have your G number and W number handy for this call so we can quickly and correctly identify you.

• What happens if I choose not to go ahead with having a test?
We may still recommend screening to you as explained earlier in this leaflet.
You can change your mind and decide not to have the test at any time before the result is given.

Other factors to consider

Insurance and Genetics

For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. The types of policy that require a medical history or genetic test are likely to be, life cover, critical illness insurance and income protection insurance.
We would suggest that if yourself or family members are considering taking out new insurance policies in the future that consideration be given to the possible affect genetic test results could have on the ability to gain insurance or the premiums charged. Genetic Test results do not affect insurance policies already in place.
The Association of British Insurers (ABI) has a Code of Practice ‘The Concordat and Moratorium on Genetic and Insurance’.

• Insurance companies cannot ask for the Predictive Genetic Test results of individuals or family members (unless for Huntington Disease over £500,000). A Predictive Genetic Test is where an individual has a family member with a genetic condition, but who personally has no symptoms, signs or abnormal medical tests consistent with the condition at time of testing.

• If a family member has been diagnosed with a genetic condition based on a Diagnostic Genetic Test then you or family members will need to mention this when asked to provide your family’s medical history. In many cases Diagnostic Genetic Testing is used to confirm a diagnosis when a particular condition is suspected because of symptoms, signs or abnormal non-genetic tests including unusual findings on a routine blood test or other test.

Sources of Further Information on insurance and genetics:

The Association of British Insurers Genetics Frequently Asked Questions https://www.abi.org.uk/products-and-issues/topics-and-issues/genetics/genetics-faqs/
Genetic Alliance UK (Charity) Genetics & Insurance http://www.geneticalliance.org.uk/information/living-with-a-genetic-condition/insurance-and-genetic-conditions/

Family planning

Everyone who has an inherited genetic condition can choose from a variety of options to ensure they do not pass it on. It is a highly personal decision and there is certainly no expectation that couples have to do anything to prevent passing on a Lynch syndrome gene alteration, but for couples who wish to consider this, some of the choices can include:

• Preimplantation genetic diagnosis (PGD)

Pre-implantation genetic diagnosis (PGD) is a special type of in vitro fertilisation (IVF) which is available to couples who are at an increased risk of having a child with a specific genetic condition. The aim is to avoid passing on the genetic condition to the child.
More information can be obtained at

https://www.guysandstthomas.nhs.uk/our-services/pgd/about-us/welcome.aspx

• Adoption
• Sperm or egg donation: dependent on who carries the gene alteration.
  Our experience is however that very few couples who carry a Lynch syndrome gene alteration choose any of the above options.

We hope you find this leaflet useful and please do not hesitate to discuss any of the issues identified in this leaflet with the genetics practitioner that is looking after you:

Liverpool Centre for Genomic Medicine Liverpool Women’s Hospital NHS Foundation Trust Crown Street Liverpool L8 7SS

 

Telephone: 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net

 

Useful websites

Genetic Alliance UK  www.geneticalliance.org.uk

Cancer research group UK (CRUK)  www.cruk.org.uk

National Institute for Health Care and Excellence (NICE) https://www.nice.org.uk/Guidance/NG151  Please also see the tools and resources section for a decision aid called ‘Lynch syndrome: should I take aspirin to reduce my chance of getting bowel cancer?’

http://www.capp3.org for research updates regarding aspirin and Lynch syndrome

https://www.ukcgg.org select ‘info & education’, then ‘documents and websites’ then Lynch syndrome Gene Specific Guidelines

 

The leaflet is detailed below, or you can download the 'Genomic Testing – Cancer Panel' leaflet in PDF.

Introduction

Cancer is common in the general population with 1 in 2* people being diagnosed with a cancer in their lifetime and most cancer occurs just by chance.  Our suspicions of an inherited explanation for the cancers in a family are raised if the same or related cancers occur in several family members on the same side of the family, usually across different generations and at a younger age than expected. This is why genetic testing would be offered to a family.

*Cancer research UK (2015) Estimated Lifetime Risk of being diagnosed, people born after 1960

What are genes and chromosomes?

Humans are made up of trillions of cells.  At the centre of almost all of our cells is a ball-shaped structure called the nucleus, inside of which are 46 thread-like structures called chromosomes. Chromosomes are long strands of DNA (DeoxyriboNucleic Acid). It is estimated that if a strand of DNA was stretched out, it would be around two metres long, even though the average cell is smaller than a pinhead.    

We have 23 pairs of chromosomes; one of each pair is inherited from your mother and one of each pair from your father. Chromosomes 1-22 are arranged in size order with number 1 being the largest and 22 the smallest. The 23rd pair of chromosomes determines if you are a male or female. Males are XY and females are XX. Chromosomes contain an estimated 20-30,000 pairs of genes that make us who we are. As we have pairs of chromosomes we therefore have pairs of genes.

Genes are often called the blueprint for life because they tell each of your cells what to do and when to do it. For example, some genes determine how tall you will be; some what colour your hair will be; some genes are responsible for maintenance in our bodies and some for our development, and so on. Genes do this by making proteins. In fact, a gene may act by being a ‘recipe’ or a code for making a certain protein. In order for a gene to do the job it is supposed to do, the ‘recipe’ or code needs to be written correctly. If the ‘recipe’ is wrong, the protein is either not made, or is made incorrectly so cannot do the job it is supposed to do.  This is sometimes called a gene alteration, a spelling mistake or a gene mutation.

What is panel testing?

Traditionally, genetic tests were targeted at just one gene. This meant that the health professional providing your care needed to have a strong idea of what was causing the cancers in a family in order to choose the correct test. This is not always possible with cancers that may not fit an obvious pattern or when the cancers could be caused by changes in one of a large number of genes. In many instances that meant multiple tests of several genes over a period of time, and more laboratory time and effort was needed to obtain a result. With new technologies it is possible to examine many different genes at the same time. 

Targeted panel testing is a technique in which a number of specific genes that are linked to a particular cancer or related cancers are examined at the same time.

If I undergo panel testing, what will my results show?

Your results will show one of 3 things:

1. A gene alteration is identified in your sample that is known to be disease causing (pathogenic). This is highly likely to be the cause of the cancers in your family. Usually we know this because it has been found in many others with the same cancer. This gene alteration may also confer other increased risks and your genetic counsellor or doctor will discuss this with you when they provide you with your results. Finding a gene alteration allows other family members to be offered predictive testing. Predictive testing is offered to family members who are known to be at risk of inheriting a gene alteration that has been identified in the family but are currently well.
2. No pathogenic gene alteration is identified. This does not necessarily mean there is not an inherited genetic explanation for the cancers in your family but it may be that within the confines of current technology we have been unable to detect a gene alteration. Alternatively there may be an alteration in a gene that we do not yet know about and therefore, cannot test for. Regardless of the results of any genetic testing we may still make screening recommendations for family members based on the family history to help protect their health.
3. A gene alteration has been found but we are not sure if it is significant or not. This is also sometimes called a variant of unknown significance (VUS) or an unclassified variant (UV). Finding this may mean we have to undertake more testing in the family or that we may need to look at the VUS again sometime in the future to see if any further information about it is available. This will be discussed with you in more detail should this be the case.

*NB: The finding of a pathogenic (disease-causing) gene alteration is based on current knowledge. Very occasionally, new information in the future may mean that our understanding of the significance of a specific gene alteration may change.*

It is very important to remember that the genes we test can also be associated with a whole range of other problems that can impact your health and may mean you need additional screening or other tests.

In general, your genetic counsellor or doctor may think it is helpful to tell you about anything that is found that is actionable. This means that there is known to be a risk to your health and your genetic counsellor or doctor can advise you about screening or treatment that could be helpful to prevent or treat the condition.

There is also a possibility that you could be found to have a gene alteration that does not affect your own health but may result in an increased risk of having an affected child. For example, some genetic conditions (called autosomal recessive conditions) arise when a child inherits a gene alteration from both parents and has no normal copy of that gene. Healthy carrier parents have one normal and one faulty copy of the gene and do not usually have any problems associated with the condition. A genetic test may indicate you are a healthy carrier of a condition, and if so you will be given information about what this means for your family.

How are gene alterations passed down (inherited) through families?

Gene alterations can be passed down by several different patterns of inheritance. The specific inheritance pattern helps us to inform the chance of other family members being found to have the same gene alteration and therefore their chance of developing cancer(s).

Your genetic counsellor or doctor will provide you with information and additional leaflets about the inheritance patterns relevant to the genes in the panel test that is being offered to you.

What are the issues to think about when deciding whether or not to go ahead with genetic testing?

A genetic test can establish whether you have an alteration in a gene which could affect your health. It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations and many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.

There are reasons for and against having a genetic test. Within one family, relatives often have different views. You should try to make your own decision, without feeling pressured from relatives or other influences. You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor. Some of the things people may consider include:

Do I need to tell people I am considering genetic testing?

It is entirely up to you whether or not you choose to tell anyone you are going ahead with genetic testing. It is often useful to have someone to accompany you to your appointments so that you have another ‘set of ears’ to hear the information and discussions that you have had. They can also be useful as a support for any discussions away from the appointment and should be someone you trust. People often choose this to be their partner, a close friend or another family member. However, if you choose to bring a family member it is important to remember the discussions you have in clinic are likely to have implications for them as well and they may not be prepared for this.  Our experience, however, has demonstrated that families are often aware of the cancers and may already be asking questions about why and so it may be that an opportunity to discuss this within the family could happen quite naturally anyway.

Other people would rather wait until there is something to know before discussing things with the wider family, whilst other people prefer to discuss things as the process goes along to help prepare the family for any news. There are no right or wrong answers and we are happy to discuss how to involve your family if you wish.

Do my family need to know about any results I receive from genetic testing?

Genetic testing provides information for the individual but also will provide information for the rest of the family. If genetic testing identifies a gene alteration in you we would assume that you had inherited it from either your mother or father. Altered genes can often be passed down through families over generations without being noticed. Therefore, finding a gene alteration in you will have implications for other family members as well and so sharing genetic information in a family is really important. It can provide family members with a real opportunity to protect their health, for example by enrolling in screening programmes or even surgical options.

Sometimes people may think if genetic testing does not show anything then there is nothing to tell anyone. However, knowing what is happening in the family can prevent work being repeated as sometimes lots of family members are asking the same questions. It is also very important to remember that, regardless of the results of any genetic testing, the family history itself may mean family members are at a higher risk of cancer anyway and opportunities to protect their health can be offered to them.

How can I share this information?

On a practical level, you will have this leaflet to share with them and we will also provide a letter after your clinic appointment detailing any other issues discussed.

If a gene alteration is found we will provide you with a ‘Dear Family Member Letter’ detailing that a gene alteration has been identified in the family, that they are at risk and how to access testing. We will also guide you as to whom the letter should be passed on to.

On an emotional level, telling family members may be more difficult. You may be worried about upsetting them or have trouble deciding when the right time is. There really is no right or wrong answer to this but it is really useful to think about this before you get your test results and we are more than happy to discuss this with you further.

Should I tell my children?

As parents, we want to protect our children from things that we believe can harm them and sometimes this means that we try and ‘hide’ things we think may be difficult for them to cope with. However, we tend to underestimate what children have already picked up on and they are often aware of something going on anyway. They may have noticed letters from the hospital or overheard conversations, they may also pick up cues from adults that they should not ask any questions.

Children in this situation may imagine something really awful is going on, often much worse than the reality, and may even believe it is something bad they have done.  Children value being included and are helped by adults who are honest and direct with communication. It is not always easy but children often cope a lot better than we give them credit for. Our experience has also shown us that the parents of adult children often do the same.

We are happy to talk to you about sharing information with your children during your appointment.                                                                                          

Who else should I tell?

That is entirely up to you. There is generally no obligation to tell your employer but it might be useful if you anticipate you may need time off work to have screening.

Having friends to discuss this with is helpful for some people but it is important to be aware that people may have differences of opinion that could be in conflict with any decisions you have made. However, for the majority of people, having discussions with other people is helpful and supportive.

What happens if I choose to go ahead and have a test?

After you have discussed what genetic testing could mean for you, you may decide to go ahead with testing. We will ask you to provide your consent and we will arrange for you to have a blood sample taken.

The laboratory team will then extract the DNA from your blood sample. They will search through the DNA of the specific set of genes on the panel to see if the code in any of these genes differs from that of a normal gene. Often, genes are large and can take a long time to be looked through. The time that we would expect results to be ready in differs between panel tests and your genetic counsellor or doctor will advise you on this.

You can discuss with your genetic counsellor or doctor how you wish to receive your results. Some people want their results by letter or over the telephone with the opportunity of a follow-up appointment to discuss any findings, whereas others prefer to come into clinic to have the opportunity to discuss the implications of any findings and next steps. This is entirely up to you and will be discussed during your appointment.

IF, FOR SOME REASON YOU HAVE NOT RECIEVED YOUR RESULTS WITHIN THE EXPECTED TIMEFRAME GIVEN TO YOU, PLEASE CALL THE LIVERPOOL CENTRE FOR GENOMIC MEDICINE ON 0151 802 5008. Please remember to have your G number and W number handy for this call so we can quickly and correctly identify you. These numbers can be found on any letter sent from the Genetics Department.

What happens if I choose not to go ahead with having a test?

We will not be able to offer predictive testing to your relatives but we may be able to make screening recommendations for your relatives based on the family history.

Attending your appointment with Genomic Medicine does not oblige you to go ahead with testing and, if you do go ahead and change your mind about receiving your results, you can do so until you are ready.

Insurance and Genetics

For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. The types of policy that require a medical history or genetic test are likely to be, life cover, critical illness insurance and income protection insurance.

We would suggest that if yourself or family members are considering taking out new insurance policies in the future that consideration be given to the possible affect genetic test results could have on the ability to gain insurance or the premiums charged. Genetic Test results do not affect insurance policies already in place.

The Association of British Insurers (ABI) has a Code of Practice ‘The Concordat and Moratorium on Genetic and Insurance’.

• Insurance companies cannot ask for the Predictive Genetic Test results of individuals or family members (unless for Huntington Disease over £500,000). A Predictive Genetic Test is where an individual has a family member with a genetic condition, but who personally has no symptoms, signs or abnormal medical tests consistent with the condition at time of testing.
• If a family member has been diagnosed with a genetic condition based on a Diagnostic Genetic Test then you or family members will need to mention this when asked to provide your family’s medical history. In many cases Diagnostic Genetic Testing is used to confirm a diagnosis when a particular condition is suspected because of symptoms, signs or abnormal non-genetic tests including unusual findings on a routine blood test or other test.

Sources of Further Information Include

The Association of British Insurers Genetics Frequently Asked Questions https://www.abi.org.uk/products-and-issues/topics-and-issues/genetics/genetics-faqs/

Genetic Alliance UK (Charity) Genetics & Insurance http://www.geneticalliance.org.uk/information/living-with-a-genetic-condition/insurance-and-genetic-conditions/

We hope you find this leaflet useful and please do not hesitate to discuss any of the issues identified in this leaflet with the genetics practitioner that is looking after you.

 Useful websites

Genetic Alliance UK

www.geneticalliance.org.uk

 

All images in this leaflet were provided by NHS National Genetics and Genomics Education Centre

 

 

 

 

 

 

The leaflet is detailed below, or you can download the 'Genomic Testing - Non-Cancer Panel' leaflet in PDF.

Introduction

For many people with a genetic condition finding out the cause of the condition can be important.  Understanding the genetic basis of the condition might help health professionals to give you information about the progress of the condition, possible preventive actions or treatment. Individuals with a genetic condition may just find it helpful to know why their signs and symptoms occur.  

What are genes and chromosomes?

Humans are made up of trillions of cells.  At the centre of almost all of our cells is a ball-shaped structure called the nucleus, inside of which are 46 thread-like structures called chromosomes. Chromosomes are long strands of DNA (DeoxyriboNucleic Acid). It is estimated that if a strand of DNA was stretched out it would be around two metres long, even though the average cell is smaller than a pinhead.    

We have 23 pairs of chromosomes; one of each pair is inherited from your mother and one of each pair from your father. Chromosomes 1-22 are arranged in size order with number 1 being the largest and 22 the smallest. The 23rd pair of chromosomes determines if you are a male or female. Males are XY and females are XX. Chromosomes contain an estimated 20-30,000 pairs of genes that make us who we are. As we have pairs of chromosomes we therefore have pairs of genes.

Genes are often called the blueprint for life because they tell each of your cells what to do and when to do it. For example, some genes determine how tall you will be; some what colour your hair will be; some genes are responsible for maintenance in our bodies and some for our development, and so on. Genes do this by making proteins. In fact, a gene may act by being a ‘recipe’ or a code for making a certain protein. In order for a gene to do the job it is supposed to do, the ‘recipe’ or code needs to be written correctly. If the ‘recipe’ is wrong, the protein is either not made or is made incorrectly so cannot do the job it is supposed to do.  This is sometimes called a gene alteration, a spelling mistake or a gene mutation.

What is panel testing?

Traditionally genetic tests were targeted at just one gene. This meant that the health professional providing your care needed to have a strong idea of what was causing the condition in order to choose the correct test. This is not always possible with conditions that may not fit an obvious pattern or when the condition could be caused by changes in one of a large number of genes. In many instances that meant multiple tests of several genes over a period of time, and more laboratory time and effort was needed to obtain a result. With new technologies it is possible to examine many different genes at the same time. 

Targeted panel testing is a technique in which a number of specific genes that are linked to a particular genetic condition are examined at the same time. Examples of conditions for which targeted gene panels have been developed are hearing impairment, epilepsy and eye disorders, which may be caused by alterations in one of many separate genes. With this test, even though we might be looking at a number of different genes, the analysis is targeted on the specific condition present in the family.

It is important to remember that the genes we test can also be associated with a range of other problems that can impact your health and may mean you need additional screening or other tests.

If I undergo panel testing, what will my results show?

Your results will show one of 3 things:

1. A gene alteration is identified in your sample that is known to be disease causing (pathogenic). This is highly likely to be the cause of your condition or contributes to it in some way. Usually we know this because it has been found in many others with the same condition. Finding a gene alteration allows other family members to be offered predictive testing. Predictive testing is offered to family members who are known to be at risk of inheriting a gene alteration that has been identified in the family but are currently well.
2. No pathogenic gene alteration is identified. This does not necessarily mean there is not an inherited genetic explanation for your condition but it may be that, within the confines of current technology, we have been unable to detect a gene alteration. Alternatively, there may be an alteration in a gene that we do not yet know about and therefore, cannot test for. Regardless of the results of any genetic testing we may still make screening recommendations for family members based on the family history to help protect their health.
3. A gene alteration has been found but we are not sure if it is significant or not. This is also sometimes called a variant of unknown significance (VUS) or an unclassified variant (UV). Finding this may mean we have to undertake more testing in the family or that we may need to look at the VUS again sometime in the future to see if any further information about it is available. This will be discussed with you in more detail should this be the case.

*NB: The finding of a pathogenic (disease-causing) gene alteration is based on current knowledge. Very occasionally, new information in the future may mean that our understanding of the significance of a specific gene alteration may change.*

It is very important to remember that the genes we test can also be associated with a whole range of other problems that can impact your health and may mean you need additional screening or other tests.

In general, your genetic counsellor or doctor may think it is helpful to tell you about anything that is found that is actionable. This means that there is known to be a risk to your health and your genetic counsellor or doctor can advise you about screening or treatment that could be helpful to prevent or treat the condition.

There is also a possibility that you could be found to have a gene alteration that does not affect your own health but may result in an increased risk of having an affected child. For example, some genetic conditions (called autosomal recessive conditions) arise when a child inherits a gene alteration from both parents and has no normal copy of that gene. Healthy carrier parents have one normal and one faulty copy of the gene and do not usually have any problems associated with the condition. A genetic test may indicate you are a healthy carrier of a condition, and if so you will be given information about what this means for your family.

How are gene alterations passed down (inherited) through families?

Gene alterations can be passed down by several different patterns of inheritance. The specific inheritance pattern helps us to inform the chance of other family members being found to have the same gene alteration and therefore their chance of developing a particular condition.

Your genetic counsellor or doctor will provide you with information and additional leaflets about the inheritance patterns relevant to the genes in the panel test that is being offered to you.

What are the issues to think about when deciding whether or not to go ahead with genetic testing?

A genetic test can establish whether you have an alteration in a gene which could affect your health. It can be difficult to make a decision about whether or not to have a genetic test. We all have gene alterations and many of these do not affect our health. It is still quite unusual for a person to know they have an alteration in a specific gene.

There are reasons for and against having a genetic test. Within one family relatives often have different views. You should try to make your own decision without feeling pressured from relatives or other influences. You will have plenty of opportunity to talk through the issues surrounding the test with the genetic counsellor or doctor. Some of the things people may consider include:

Do I need to tell people I am considering genetic testing?

It is entirely up to you whether or not you choose to tell anyone you are going ahead with genetic testing. It is often useful to have someone to accompany you to your appointments so that you have another ‘set of ears’ to hear the information and discussions that you have had. They can also be useful as a support for any discussions away from the appointment and should be someone you trust.

People often choose this to be their partner, a close friend or another family member. However, if you choose to bring a family member it is important to remember the discussions you have in clinic are likely to have implications for them as well and they may not be prepared for this.  Our experience, however, has demonstrated that families are often aware of the family history and may already be asking questions about why and so it may be that an opportunity to discuss this within the family could happen quite naturally anyway.

Other people would rather wait until there is something to know before discussing things with the wider family, whilst other people prefer to discuss things as the process goes along to help prepare the family for any news. There are no right or wrong answers and we are happy to discuss how to involve your family if you wish.

Do my family need to know about any results I receive from genetic testing?

Genetic testing provides information for the individual but will also provide information for the rest of the family. If genetic testing identifies a gene alteration in you we would assume that you had inherited it from either your mother or father. Altered genes can often be passed down through families over generations without being noticed. Therefore, finding a gene alteration in you will have implications for other family members as well and so sharing genetic information in a family is really important. It can provide family members with a real opportunity to protect their health, for example, by enrolling in screening programmes or even surgical options.

Sometimes people may think if genetic testing does not show anything then there is nothing to tell anyone. However, knowing what is happening in the family can prevent work being repeated as sometimes lots of family members are asking the same questions. It is also very important to remember that, regardless of the results of any genetic testing, the family history itself may mean family members are at a higher risk of a condition anyway and opportunities to protect their health can be offered to them.

How can I share this information?

On a practical level you will have this leaflet to share with them and we will also provide a letter after your clinic appointment detailing any other issues discussed.

If a gene alteration is found we will provide you with a ‘Dear Family Member Letter’ detailing that a gene alteration has been identified in the family, that they are at risk and how to access testing. We will also guide you as to whom the letter should be passed on to.

On an emotional level telling family members may be more difficult. You may be worried about upsetting them or have trouble deciding when the right time is. There really is no right or wrong answer to this but it is really useful to think about this before you get your test results and we are more than happy to discuss this with you further.

Should I tell my children?

As parents, we want to protect our children from things that we believe can harm them and sometimes this means that we try and ‘hide’ things we think may be difficult for them to cope with. However, we tend to underestimate what children have already picked up on and they are often aware of something going on anyway. They may have noticed letters from the hospital or overheard conversations, they may also pick up cues from adults that they should not ask any questions.

Children in this situation may imagine something really awful is going on, often much worse than the reality, and may even believe it is something bad they have done.  Children value being included and are helped by adults who are honest and direct with communication. It is not always easy but children often cope a lot better than we give them credit for. Our experience has also shown us that the parents of adult children often do the same.

We are happy to talk to you about sharing information with your children during your appointment.                                                                                                   

Who else should I tell?

That is entirely up to you. There is generally no obligation to tell your employer but it might be useful if you anticipate you may need time off work to have screening.

Having friends to discuss this with is helpful for some people but it is important to be aware that people may have differences of opinion that could be in conflict with any decisions you have made. However, for the majority of people, having discussions with other people is helpful and supportive.

What happens if I choose to go ahead and have a test?

After you have discussed what genetic testing could mean for you, you may decide to go ahead with testing. We will ask you to provide your consent and we will arrange for you to have a blood sample taken.

The laboratory team will then extract the DNA from your blood sample. They will search through the DNA of the specific set of genes on the panel to see if the code in any of these genes differs from that of a normal gene. Often, genes are large and can take a long time to be looked through. The time that we would expect results to be ready differs between panel tests and your genetic counsellor or doctor will advise you on this.

You can discuss with your genetic counsellor or doctor how you wish to receive your results. Some people want their results by letter or over the telephone with the opportunity of a follow-up appointment to discuss any findings whereas others prefer to come into clinic to have the opportunity to discuss the implications of any findings and next steps. This is entirely up to you and will be discussed during your appointment.

IF, FOR SOME REASON, YOU HAVE NOT RECIEVED YOUR RESULTS WITHIN THE EXPECTED TIMEFRAME GIVEN TO YOU PLEASE CALL THE LIVERPOOL CENTRE FOR GENOMIC MEDICINE ON 0151 802 5008. Please remember to have your G number and W number handy for this call so we can quickly and correctly identify you. These numbers can be found on any letter sent from the Genetics Department.

What happens if I choose not to go ahead with having a test?

We will not be able to offer predictive testing to your relatives but we may be able to make screening recommendations for your relatives based on the family history.

Attending your appointment with Genomic Medicine does not oblige you to go ahead with testing and, if you do go ahead and change your mind about receiving your results, you can do so until you are ready.

Insurance and Genetics

For some types of insurance it is necessary to provide medical information, including genetic information, to the insurers in order for them to set up your policy and work out your premiums. The types of policy that require a medical history or genetic test are likely to be, life cover, critical illness insurance and income protection insurance.

We would suggest that if yourself or family members are considering taking out new insurance policies in the future that consideration be given to the possible affect genetic test results could have on the ability to gain insurance or the premiums charged. Genetic Test results do not affect insurance policies already in place.

The Association of British Insurers (ABI) has a Code of Practice ‘The Concordat and Moratorium on Genetic and Insurance’.

• Insurance companies cannot ask for the Predictive Genetic Test results of individuals or family members (unless for Huntington Disease over £500,000). A Predictive Genetic Test is where an individual has a family member with a genetic condition, but who personally has no symptoms, signs or abnormal medical tests consistent with the condition at time of testing.
• If a family member has been diagnosed with a genetic condition based on a Diagnostic Genetic Test then you or family members will need to mention this when asked to provide your family’s medical history. In many cases Diagnostic Genetic Testing is used to confirm a diagnosis when a particular condition is suspected because of symptoms, signs or abnormal non-genetic tests including unusual findings on a routine blood test or other test.

Sources of Further Information Include

The Association of British Insurers Genetics Frequently Asked Questions  https://www.abi.org.uk/products-and-issues/topics-and-issues/genetics/genetics-faqs/

Genetic Alliance UK (Charity) Genetics & Insurance http://www.geneticalliance.org.uk/information/living-with-a-genetic-condition/insurance-and-genetic-conditions/

We hope you find this leaflet useful and please do not hesitate to discuss any of the issues identified in this leaflet with the genetics practitioner that is looking after you.

Useful websites

Genetic Alliance UK

www.geneticalliance.org.uk

 

All images in this leaflet were provided by NHS National Genetics and Genomics Education Centre

 

This leaflet is detailed below The leaflet is detailed below, or you can download the 'Liverpool Centre for Genomic Medicine (LCGM) A guide to your referral'  leaflet in PDF.

This leaflet provides important information to help people who are referred to us. It aims to answer some of the common questions we are asked.

Why have I been referred to Liverpool Centre for Genomic Medicine?

Genomic medicine is the medical specialty for individuals or families with, or at risk of, conditions which may have a genetic basis. Genetic disorders can affect any body system and any age group.

Before your appointment

We offer different types of appointments in different hospitals in the region. You may see a Doctor or Genetic Counsellor in clinic, and we also offer telephone and video appointments.

Therefore, we ask patients to carefully note the time, date and location of their appointment to avoid missing it.

We will always try and provide you an appointment that is closest to you but this is not always possible due to waiting times or suitability e.g. some of our clinics are only suitable for children.

Please note: our clinic rooms at the Liverpool Women’s Hospital are in the antenatal clinic. If you feel it would be difficult for you to be seen in an antenatal department please ring and we may be able to offer you an appointment at one of our other clinic sites.

Family History Collection Team (FHCT)

The FHCT may contact you before your appointment.  Their job is to gather information in preparation for your appointment to make the appointment as useful as possible.  They may take details of people in your family who have had genetic testing, draw a family tree or make a note of the growth and development of your child.  The FHCT are non-clinical members of staff and will not be able to answer any questions in relation to the reason you have been referred to LCGM. However, they can note down any specific questions you would like answering in your appointment. 

What if I have a disability such as a visual or hearing impairment or I need support to get to or at an appointment or I need a translator?

Please ring or email us to let us know if you require additional support in your appointment and we will do our best to accommodate your needs.  See contact details below.

Parking

Parking availability and cost of parking varies. Please check where your appointment is and look at that hospital’s website for parking details.

At my appointment

You will be seen by a member of the genomic medicine team. This may be a Doctor who specialises in genetics or a Genetic Counsellor.

Most genetic appointments are 45 to 60 minutes long, so you should not feel rushed. We are happy for friends or family to attend with you to provide support.

What happens in your appointment will vary depending on the reason for your referral but may include:

• A detailed discussion of the reason that has brought you to the clinic
• The drawing of a family tree (if not drawn up beforehand) and medical details of relatives may be asked about (such as the cause and age of their death). It is useful to have found out these details before you come to the clinic or bring a relative who will know. ·
• A medical examination may be carried out if appropriate.

The doctor/genetic counsellor will explain their assessment to you and discuss your options and choices. You will be encouraged to ask questions and to make your own decisions.

In some situations, tests (such as blood tests) may be offered. Some tests are available on the day of your appointment, but often you will be asked to take some time to make a decision and come back. The results from genetic testing often take several weeks to several months, so, even if you have a blood sample taken on the day of your appointment, you will not receive any results the same day.

At the end of the appointment a plan will be made. This may include information gathering, special tests and/or another appointment

My child has been referred to the LCGM, should I bring them to the appointment?

Your child will need to come to the appointment if an examination is required. However, we can offer you another appointment without your child if you have any questions, you would rather not ask in front of them. We always encourage children to be involved in their appointment and we will not offer genetic testing to a child without including them in any discussions if possible. We will always try and tailor the appointment to be age appropriate.

After your appointment

We will send you a summary letter. If anything in this is unclear, please do not hesitate to contact the department with any queries.

Please note: there is an option to have your letter and any other correspondence sent via email. Do not hesitate to ask your clinician for this option if you have not been asked.

We will write to your GP and the referring doctor unless you specifically ask us not to do so. If genetic tests have been done, we will arrange to give you the results once they are available. Arrangements may be suggested for other family members to be referred.

Where else can I get information before my appointment?

Liverpool Women’s Hospital Website: www.liverpoolwomens.nhs.uk

NHS Choices: https://www.nhs.uk

Genetic Alliance: https://geneticalliance.org.uk/

Cancer Research UK: Cancer Research UK

Feedback welcome

We strive to continually improve the service we deliver in the best way we can and your feedback is very important to us. You will receive a ‘friends and family’ text after your appointment which will provide you with the opportunity to feedback your experience. Comments, suggestions and complaints can also be made through PALS. Call 0151 702 4353 or email PALS@lwh.nhs.uk

If you need more advice about any aspect of your referral into Genomic Medicine, you are welcome to contact:

Liverpool Centre for Genomic Medicine

Liverpool Women’s Hospital NHS Foundation Trust

Crown St. Liverpool, Merseyside L8 7SS

Telephone 0151 802 5001 or 5008             

Email: lwft.clingen@nhs.net