BRCA gene mutations in men and women: addressing misconceptions to help improve outcomes in cancer

We all possess certain genes that help protect against cancer, and BRCA genes are just one example. Everyone is born with two BRCA genes (BRCA1 and BRCA2) which, contrary to some opinions, do not cause cancer but instead protect us from it.

Acting as in-built ‘tumour suppressors’, these genes continually repair any damage to our DNA which can naturally occur when our cells divide or which can be induced by external factors.1,2 It is possible for these BRCA genes to become mutated, preventing them from carrying out their usual function and increasing the risk of cancer.1,2



Since the discovery of BRCA1 and BRCA2, significant medical advances have been made in terms of understanding the role these genes play in the risk of developing certain types of cancer. This led to the development of testing and targeted or ‘personalised’ cancer treatments.3 These treatments are designed to potentially help improve outcomes for people carrying these specific gene mutations.3

Although BRCA genes in women has received a lot of media attention in recent years, there remains a fundamental gap in awareness around BRCA mutations in men.4 The truth is that men are just as likely as women to have a BRCA mutation5 and are equally likely to pass it to their children.6 BRCA1 or BRCA2 genes have been linked to an increased risk breast, pancreatic, prostate and ovarian cancer, amongst other cancers, all of which (aside from ovarian cancer) affect men.7 These mutations aren’t always rare either, as, depending on the population, between 1 in 40 and 1 in 400 people carry a mutation in BRCA1 or BRCA2.8

Although the most extensive research has been conducted into BRCA mutations in breast and ovarian cancers, new scientific evidence is building around the role that BRCA mutations play in other cancers. For example, evidence suggests:

•       BRCA2 mutations are associated with a 5-10% lifetime risk of developing pancreatic cancer9 and 20-25% lifetime risk for developing prostate cancer10

•       BRCA1/2 associated prostate cancers have been reported to be more aggressive than those not associated with a BRCA mutation11

•       The risk of male breast cancer by aged 70 is increased to approximately 3.2 - 12% with a BRCA2 mutation and 0.22 - 2.8% with a BRCA1 mutation, compared to 0.1% in the general population7,12

Misconceptions around BRCA mutations are further perpetuated by the fact that BRCA stands for ‘breast cancer suppressor gene’ and the term for the passing down of this genetic mutation is commonly known as ‘hereditary breast and ovarian cancer syndrome’ (HBOC).7 Although the name is logical, given that BRCA gene mutations were originally discovered in breast cancer patients as increasing their cancer risk, the confusion has led to a suggested rename of the syndrome. Recent discussions have suggested changing the name to ‘King Syndrome’ (after Mary-Claire King, the geneticist who first discovered BRCA1), to help address this issue and consequently increase appropriate testing and timely access to the appropriate treatment options for all cancer patients with BRCA gene mutations.13

As part of AstraZeneca’s commitment to helping improve the outcomes of cancer patients worldwide, we believe it is vital to ensure that the latest scientific understanding is made as clear and accessible as possible, to help ensure it is adequately reflected in the real-world diagnosis and care of people with cancer. BRCA mutations are no exception. Although progress is being made every day, there is still much further to go.

New research is being conducted and novel therapies are constantly being investigated that can utilise BRCA mutations as a weakness of cancers, but it is essential that misconceptions about the gene do not act as roadblocks to the progression of medicine. With this in mind, perhaps every individual worldwide has the power to play an important role in tackling the growing global cancer burden, by simply remaining curious about the science and sharing what you have learnt with the people that you care about.

While research is being conducted and new cancer treatments are being discovered, progress is only really attained if this is valued and more information is made accessible to the very people it is designed to help. It would be a grave shame for misconceptions, like those around BRCA mutations, to be a stumbling block.

Key facts:

•       Depending on the population, between 1 in 40 and 1 in 400 people carry a mutation in BRCA1 or BRCA28

•       Men are just as likely as women to have a BRCA mutation5

•       BRCA1 or BRCA2 genes are linked to an increased risk of breast, pancreatic, prostate and other cancers, all of which (aside from ovarian cancer) affect men6,7

•       BRCA2 mutations are associated with an approximate 5-10% lifetime risk of developing pancreatic cancer (based on a US study)9 and an estimated 20-25% lifetime risk for developing prostate cancer (based on a UK study)10

•       BRCA1/2 associated prostate cancers have been reported to be more aggressive than those not associated with a BRCA mutation11

•       The risk of male breast cancer by aged 70 is increased to approximately 3.2-12% with a BRCA2 mutation and 0.22 - 2.8% with a BRCA1 mutation, compared to 0.1% in the general population 7,12

 

Reference

  1. Genetics Home Reference. (2019). BRCA1 gene. Available at: https://ghr.nlm.nih.gov/gene/BRCA1 [Accessed September 2019].
  2. Genetics Home Reference. (2019). BRCA2 gene. Available at: https://ghr.nlm.nih.gov/gene/BRCA2 [Accessed September 2019].
  3. Olopade, O., Grushko, T., Nanda, R. and Huo, D. (2008). Advances in Breast Cancer: Pathways to Personalized Medicine. Clinical Cancer Research, 14(24), pp.7988-7999.
  4. Skop M et al. “2018). “Guys Don’t Have Breasts”: The Lived Experience of Men Who Have BRCA Gene Mutations and Are at Risk for Male Breast Cancer. American Journal of Men's Health. 12(4), pp.961-972.
  5. Pal, T., et al. (2013). Interest of individuals from BRCA families to participate in research studies focused on male BRCA carriers. Familial Cancer, 12(4), pp.615-619.
  6. National Cancer Institute. (2019). BRCA Mutations: Cancer Risk and Genetic Testing. Available at: https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet [Accessed September 2019].
  7. Casaubon J and Regan JP. (2019). BRCA 1 and 2. StatPearls [Internet] Treasure Island (FL): StatPearls Publishing; Available at: https://www.ncbi.nlm.nih.gov/books/NBK470239/ [Accessed September 2019].
  8. Ovarian.org.uk. BRCA mutations in Jewish populations. Available at: https://ovarian.org.uk/ovarian-cancer/brca/brca-mutations-jewish-populations/  [Accessed September 2019].
  9. Pilarski, R. (2019). The Role of BRCA Testing in Hereditary Pancreatic and Prostate Cancer Families. American Society of Clinical Oncology Educational Book, (39), pp.79-86.
  10. NHS Trust. (2014). BRCA1 and BRCA2 for men. Available at: https://www.ouh.nhs.uk/patient-guide/leaflets/files/120417brca1brca2.pdf [Accessed September 2019].
  11. Na R, et al. Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death. European Urology. 71 (2017) 740-747
  12. Tai YC, et al. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007;99:1811-1814.
  13. Pritchard, C. (2019). New name for breast-cancer syndrome could help to save lives. Nature, 571(7763), pp.27-29. Available at: https://www.nature.com/articles/d41586-019-02015-7 [Accessed September 2019]

 

Veeva ID: Z4-20332    

Date of Preparation: September 2019

Date of Expiry: September 2021