Testing for BRCA

What is BRCA?

The BRCA1 and BRCA2 genes were among the first cancer genes to be identified in the 1990s. Alterations in these genes, otherwise known as mutations, increase the risk of breast, ovarian and prostate cancer (these mutations are also known to increase the risk of pancreatic cancer, melanoma, and some other cancers, though all at a low level of risk). 

While the majority of these cancers occur without any identifiable underlying genetic cause, in the UK population, approximately 5-10% of all breast and 10-15% of all ovarian cancer cases are thought to be caused by inheritance of a BRCA mutation.

Not all families with a strong history of breast, ovarian and prostate cancers have mutations in BRCA genes, as many other genes can also lead to an increased risk of these cancers.

In general, you are eligible for BRCA testing if you are classified as having a 10% or greater chance of carrying a BRCA mutation. However, the NHS automatically offers testing if you:

  • You are Ashkenazi Jewish and have had breast cancer at any age
  • You have high-grade non mucinous epithelial ovarian cancer at any age

If you would like to determine whether you are eligible for BRCA testing, talk to your GP about your family’s cancer history. If appropriate, they will refer you to your regional genetics clinic where a genetic counsellor will assess whether you are eligible, and if you are, will provide you with support and information.

To explore your risk of having inherited a gene alteration (also known as a mutation, variant or fault) that could increase your risk of developing certain cancers, and then compares this to the current NHS guidelines for genetic testing please click visit: https://ovarian.org.uk/risktool/

People with mutations in a BRCA gene are often referred to as being BRCA positive, although the term BRCA carrier is also widely used. It is important to remember that someone who is BRCA positive will NOT definitely develop cancer, however they do have a greater risk of developing it at some point in their lives relative to the general population.

As we go through life, we accumulate damage to our DNA known as mutations. BRCA genes are responsible for repairing this damage. Usually, a cell needs to develop multiple mutations before it becomes cancerous, but in most cases the BRCA1/2 proteins repair these faults as they occur, which prevents the development of cancer.

In people who are BRCA positive, the gene doesn’t function as it should. These people are therefore less able to repair DNA damage as it occurs and so are more likely to develop cancer at a younger age. For more information, see The Role of The BRCA Gene at the BRCA Alliance website.

BRCA genes are inherited in an autosomal dominant manner. This means that a person who has a mutation in either of the BRCA1 or BRCA2 genes has a 50% chance of passing on that mutation to each of their children. Men as well as women can be BRCA positive so a mutation can be passed from father to child as well as mother to child.

BRCA genes, though dominant, have incomplete penetrance. This means that someone that is BRCA positive is more likely, but not guaranteed, to develop cancer relative to someone in the general population.

Approximately 1 in 300-400 people in the UK have a mutation in their BRCA1 or BRCA2 genes. Certain people, however, are at greater risk of having BRCA mutations than others. Individuals with several close blood relatives (e.g. sister, mother, grandmother, aunt) affected with breast or ovarian cancers, and where the diagnoses of cancer occurred before the age of 50, are at greater risk.

Individuals of Ashkenazi Jewish origin are also at greater risk than the general population. It is estimated that 1 in 40 people of Ashkenazi Jewish ancestry have a mutation in a BRCA gene (link to section below).

If you have a blood relative with a known mutation in a BRCA gene and would like to understand more about your risk, talk to your GP about your family’s cancer history. If appropriate, they will refer you to your regional genetics clinic where a genetic counsellor will provide you with support and information and will discuss with you whether genetic testing is an appropriate option. This will be dependent on how closely related you are to the family members with known BRCA mutations and whether any of your family members have been affected by cancer.

Ashkenazi Jews are descended from a small population of approximately 350 individuals who lived about 700 years ago. This means that Ashkenazi Jews share a greater proportion of their genetic makeup with one another relative to others in the general UK population. This is known as a founder effect and is particularly common in small populations or ethnic minorities where individuals tend to have children with others from the same population.

It is estimated that around 1 in 40 people of Ashkenazi Jewish ancestry are BRCA positive relative to 1 in 300-400 in the general population. BRCA-associated cancers are therefore seen more frequently in Jewish people of Ashkenazi descent.

Three specific mutations within the BRCA1 and BRCA2 genes are thought to account for the majority of cases of hereditary cancer in Ashkenazi Jews. These three mutations are often called: 185delAG (also known as c.68_69delAG), 5382insC (also known as c.5266dupC), and 6174delT (also known as c.5946delT).

The likelihood of an Ashkenazi Jew inheriting a BRCA mutation depends on a number of factors including:

  • The strength of their Ashkenazi ancestry; people with four Ashkenazi Jewish grandparents have a higher risk than those with mixed Ashkenazi Jewish and non-Ashkenazi Jewish ancestry.
  • The strength of their family history of breast, ovarian or prostate cancer – the number of family members who have developed cancer, the age at which they developed cancer and how closely related they are, are all contributing factors.
  • Whether they have blood relatives with known mutations in a BRCA gene.

If you are Ashkenazi and are concerned about your risk, talk to your GP about your family’s cancer history, mentioning that you are of Ashkenazi origin. If appropriate, they will refer you to your regional genetics clinic where a genetic counsellor will provide you with support and information and will discuss with you whether genetic testing is an appropriate option.

Having a mutated version of the BRCA gene greatly increases a woman’s chance of developing breast cancer and Ovarian cancer. They also increase a man’s chance of developing breast cancer and prostate cancer.

Breast Cancer

Breast cancer is a disease in which the breast cells grow and replicate abnormally forming a mass called a tumour. These tumours are ‘malignant’ and can spread to other sites in the body replacing normal healthy tissue.

Breast cancer is very common and affects 1 in 8 women in the UK at some point during their life. It is mostly common in women over the age of 50. The NHS National Breast Screening programme offers 3 yearly mammograms to all 47-74 year old women. Men can also be affected by breast cancer, although this is rare.

BRCA mutations, particularly BRCA1, are associated with a greater risk of developing ‘triple negative’ breast cancer. Triple negative breast cancers account for approximately 10-20% of all cases of breast cancer with over one third of these cases occurring in women who are carriers of a BRCA1 mutation. For more information on triple negative breast cancer, watch this useful video. Breast cancer associated with BRCA2 mutations is usually hormone receptor positive. Triple negative breast cancer can also occur in association with BRCA2, particularly in post-menopausal women.

For more information on the risk of developing BRCA-associated breast cancer, see the table here.

Ovarian Cancer

Ovarian cancer is a disease caused by rapid growth and division of cells within one or both ovaries. Ovarian cancer is a general term that includes cancer of 30 different ovary-related tissue types.

Ovarian cancer affects 1 in 72 women in the UK, occurring most frequently in women over 60 years of age.

BRCA1 and BRCA2 mutations are associated with a greater risk of developing ‘high grade serous’ ovarian cancer. This form of cancer accounts for up to 70% of all ovarian cancer cases with approximately one quarter of these cases occurring in women who are BRCA positive. There is also evidence that ‘endometrioid’ ovarian cancer, which is characterised by disease in the womb, are also more common in women with BRCA mutations. Ovcare provides further information on types of ovarian cancer.

For more information on the risk of developing BRCA-associated ovarian cancer, see the table here.

Prostate cancer

Prostate cancer is the most common cancer in men with over 47,000 new cases diagnosed every year in the UK. It is a disease of the prostate which usually develops slowly with few symptoms in the early phases of development. Prostate cancer affects 1 in 8 men in the UK, occurring most frequently in men over 70 years of age.

Although there is evidence that being BRCA positive increases the risk of prostate cancer, mutations in BRCA1 and BRCA2 are only found in a 0.44% and 1.2% of prostate cancer cases diagnosed at under the age of 65, respectively. So, while the risk of prostate cancer is increased for men with these mutations, the majority of prostate cancer cases are not linked to BRCA1 or BRCA2 mutations. There is increasing evidence however that prostate cancer associated with such mutations may behave more aggressively and therefore should be considered for more radical treatment. Trials are ongoing to address this question.

For more information on the risk of developing BRCA-associated prostate cancer, see the table here.

If you are found to be eligible for genetic testing for BRCA, your genetic counsellor will talk to you about your potential options if your test comes back positive. This conversation will help you to decide whether taking the test is the right option for you. Making a decision about whether to go ahead with the test may be difficult and lead to feelings of anxiety or fear. Thinking about the possibility of getting cancer is difficult. It may also stir up emotions you felt when other family members were diagnosed with cancer and what they went through.

Before you decide, it can help to think about how you feel about having a test, what a positive result would mean for you and if it would have an impact on your family members. Your decision may also be affected by the availability and suitability of preventative treatment and whether this is something you would consider. Remember that it is your decision to make but talking through your options with your family and knowing how they feel may help you to make the right decision. If you decide to go ahead with testing, you will be supported by a team of specialists. You will be offered genetic counselling and you can change your mind at any time if you decide not to have a test.

If you do decide to go ahead with the test, check with your genetic counsellor about when you are likely to receive the results. It will help to have some idea, as waiting for results can be a challenging time.

In general, you are eligible for BRCA testing on the NHS if you are classified as having a 10% or greater chance of carrying a BRCA mutation.

The following factors are likely to determine whether you are eligible:

  • Your age.
  • Whether you currently have or have previously had breast, ovarian or prostate cancer.
  • If you know that a close blood relative is BRCA positive.
  • If you have a strong family history of breast, ovarian and or prostate cancer. Generally speaking, this means at least two close family members with these types of cancers on the same side of the family.
  • The nature of your family history including the number of family members who have developed these types of cancers, their gender and the age of cancer onset.
  • If you are of Ashkenazi origin.

Importantly, you are automatically eligible for testing on the NHS if:

  • You are Ashkenazi Jewish and have had breast cancer at any age
  • You have High-grade non mucinous epithelial ovarian cancer at any age

If you would like to determine whether you are eligible for BRCA testing, talk to your GP about your family’s cancer history. If appropriate, they will refer you to your regional genetics clinic where a genetic counsellor will assess whether you are eligible, and if you are, will provide you with support and information.

It is important to be aware that a strong family history of breast, ovarian and or prostate cancer does not necessarily mean that there is a BRCA mutation in your family. Cancer can be caused by a number of different genetic factors in a variety of different genes, as well non genetic factors too.

Children under the age of 18 are not eligible for carrier testing for BRCA. This is because anyone having a genetic test needs to be old enough to make their own choice about whether to have the test or not. They also need to be able to fully understand all the implications that the test results may have on them and their family members.

To explore your risk of having inherited a gene alteration (also known as a mutation, variant or fault) that could increase your risk of developing certain cancers, and then compares this to the current NHS guidelines for genetic testing please click visit: https://ovarian.org.uk/risktool/

For individuals who do not fit the criteria for testing on the NHS, it may be possible to pay for a test privately.

From early next year 2023 any person with at least one Jewish grandparent who is above the age of 18 will be able to have the BRCA genetic test free.

Please complete this form to register your interest in the NHS BRCA screening programme, and be informed about the programme once it has launched.