BBC DNA Family Secrets - genetic testing for BRCA gene variants

DNA Family Secrets is a show commissioned by the BBC and hosted by Stacey Dooley, which explores the growing popularity of genetic testing that allows people to ask questions, previously impossible to answer, about their families, ancestry, and health. Stacey Dooley meets people from across the UK, who want to unlock mysteries hidden within their genetic code.  The series works with clinical geneticists, genetic counsellors, genealogists, social workers, and other medical and non-medical professionals using the very latest DNA technology, to reveal lost heritage, track down missing relatives and detect genetic risks for debilitating diseases before it is too late.

Check4Cancer was honoured to take part in Series One (episode 2), where we conducted genetic testing for a woman called Duri who feared she may develop terminal ovarian cancer like her mother. Thankfully her results were normal.  You can view the episode here.

We were invited to take part in Series Two and Sarah Beck, a Check4Cancer genetic counsellor who has worked within the field of cancer genetics since 2001, conducted cancer genetic testing* for twins, Diane, and Louise, who were concerned due to their family history of cancer, that they had inherited a faulty gene.  You can view the episode in full here.

* Diane and Louise had already been offered additional breast screening through the NHS, but they did not meet the criteria for genetic testing in the NHS. 

Sarah Beck discusses Diane and Louise's journey with cancer genetic testing in DNA Family Secrets. 

Why did Diane and Louise think they needed to be tested for genes that would make them more suspectable to breast and ovarian cancer?

Diane and Louise are identical twins who were concerned that their family history of cancer would make them more susceptible to the disease. There had been more cases of breast and ovarian cancer in their family than we would expect to see by chance, but none of their relatives had developed cancer at a young age. When breast cancer is caused by an inherited genetic predisposition, such as a fault or variant in BRCA1 or BRCA2, then breast cancers are usually developed at a younger age. Breast cancer is common in the general population, but these cancers usually occur after the age of 50+, therefore, the chance of them having a faulty gene was less than 10%.

Their mother had breast cancer diagnosed at the age of 58 and then developed stomach cancer aged 65. She, unfortunately, lost her life six months later, aged 66.  One of their mother’s sisters had breast cancer at the age of 42 and passed away aged 73.  Diane and Louise’s maternal grandmother had breast cancer at the age of 42 and then developed breast cancer again when she was aged 53.  She passed away aged 80.  The twin’s maternal grandmother also had a sister who developed ovarian cancer aged 60 and her daughter developed breast cancer at 50 years of age and their mother’s father also had two sisters, who developed breast cancer at the ages of 40 and 50 respectively.

Due to their family history of breast and ovarian cancer, Diane and Louise were concerned that they may have a variant in the BRCA1 or BRCA2 genes (BRCA1 is the gene that Angelina Jolie had a variant in). When Sarah met with them for filming for DNA Family Secrets, they were unaware that several other genes can also be associated with an increased risk of developing breast cancer.

There is also a common misconception that the BRCA1 and BRCA2 genes are bad genes, whereas, in fact, we all have two copies of the BRCA1 gene and two copies of the BRCA2 gene.  These genes code for tumour suppressor proteins, which have a role in stopping cancer developing. However, if there is a ‘spelling mistake’ or ‘variant’ in the BRCA1 or BRCA2 genes, that tumour suppressor protein is not made properly.  This is a bit like having a spelling mistake in a recipe book.  Subsequently, variants in the BRCA1 and BRCA2 genes increase the risk of developing certain types of cancer, including breast, ovarian and prostate cancers.

You can find out more about BRCA1 and BRCA2 genes here. The likelihood of Diane and Louise having a variant in BRCA1 or BRCA2 was less than 10% and the chance of them having a variant in another gene was even less than this, as variants in the BRCA1 and BRCA2 genes are the most common cause of an inherited genetic predisposition to breast cancer.

How common is the BRCA1 and BRCA2 gene in the population?

In the general population, 1 in 400 people have a variant in BRCA1 or BRCA2 (1 in 40 in the Ashkenazi Jewish population).  Diane and Louise were more concerned about their maternal family history as their mother’s death affected them both enormously.  They were all extremely close and the twins had cared for their mother throughout her illness.  Their fear of having the ‘family cancer gene’ was further impacted by the fact that Diane has two autistic children and obviously she was very worried about their welfare if she was to develop cancer.

Most cancers are ‘multifactorial’, which means that they are caused by a combination of factors, age, genetic factors, environmental factors, and bad luck!  For some people, the environmental factors will give the greater risk, for others, genetic factors will be more important, but the same environmental factors risk apply for those with a genetic predisposition. 

How does the process of cancer genetic testing work?

The person being tested for gene variants that predispose to cancer provides a blood or saliva sample, which is then sent to a laboratory, where the DNA is extracted from the sample.

The person’s DNA is then sequenced, which means reading through the DNA, and recording the ‘sequence’ letter by letter. This sequence is then compared to a ‘normal’ sequence and any differences between the two sequences are then reported.

Any variants identified in the person’s DNA will be either:

  1. ‘benign’ with no effect on the gene function or product
  2. ‘pathogenic’ – resulting in an abnormal protein product
  3. a ‘variant of uncertain significance – at present we do not know if the variant affects the gene function or protein product.

Any variants identified with blood or saliva DNA will have been inherited/present from birth.  Testing tumour samples identifies variants in the tumour, which have happened as part of the tumour developing.

Why is genetic counselling so important before you get tested for any genetic variants for cancer?

If you are thinking of being tested for genetic variants that predispose you to developing cancer, it is very important that you understand the process and the possible results, so that you can provide informed consent for testing.

At Check4Cancer, before we do any genetic testing, a consultation is arranged to discuss your personal and/or family history of cancer, and advise you on the risks within your family, such as how likely it is that the cancers in your family have been caused by a faulty gene. The genetic counsellor would also be able to discuss your own personal risks of developing cancer or additional cancers in the future as well as the risks for other family members

The counselling process is very important as it helps you to consider how you would feel with each possible result and be certain that whatever the results are from DNA testing that you would be happy to know. It is also important to be aware of how your results may have implications for other family members and how you would feel about sharing your results with your relatives. 

After each consultation, you will be provided with a letter from your genetic counsellor to summarise all the information given, your results and any additional advice. Your genetic counsellor can also provide you with a letter for your relatives if necessary.

You can find out more about genetic counselling here.  

What were the results of cancer genetic testing for Diane and Louise? 

I’m pleased to say that as expected, their results were normal. If they did have a variant in BRCA1 or BRCA2, they would each have up to an 80% lifetime risk of developing breast cancer.  Even with identical twins who have identical DNA, there is still the chance that one of them might develop cancer and the other one doesn’t.

When should people consider having cancer genetic testing? Are there any red flags that should prompt them to be tested?

Each cancer type has different criteria for genetic testing in the UK, so the information below is taken from the National Guidelines for genetic testing for variants in the BRCA1 and BRCA2 genes. If you have any of the following diagnoses or family history, you should consider genetic counselling and testing for variants in the BRCA1 and BRCA2 genes:

  • Invasive breast cancer < 30 years
  • Bilateral breast cancer, both breasts < 50 years
  • Triple-negative breast cancer < 60 years
  • Male breast cancer at any age
  • Non-mucinous ovarian cancer at any age
  • Breast cancer < 45 years and a first-degree relative with breast cancer < 45 years
  • Three or four close relatives with breast cancer at any age
  • Ashkenazi Jewish ancestry and breast cancer at any age

For more information on Check4Cancer's cancer genetic testing and genetic counselling services, please click here.

Sarah Beck | Registered Genetic Counsellor

Sarah Beck is a Registered Genetic Counsellor who has worked within the field of cancer genetics since 2001, working for GeneHealth at Check4Cancer since 2014.

Sarah graduated from the University of Newcastle upon Tyne with a BSc (Hons) in Genetics in 2000 and in 2003, was awarded an MSc in Genetic Counselling from Manchester University.  Sarah gained AGNC (Association of Genetic Nurses and Counsellors) professional registration in 2006 and HGSA (Human Genetics Society of Australasia) registration in 2009 whilst working as a Genetic Counsellor in Auckland, New Zealand for three years. 

Sarah has previously worked for the NHS Clinical Genetics Services in Oxford, Cambridge and Southampton and she also worked on the CAPP2 Lynch Syndrome cancer prevention study in Newcastle.  Sarah is a GCRB sign-off mentor and assessor for new Genetic Counsellors seeking GCRB registration.