Genetics and Ovarian Cancer
Genetic mutations and hereditary conditions have a key role in increasing the risk of ovarian cancer risk. The most well-known are mutations in the BRCA1 and BRCA2 genes, which significantly increase the likelihood of developing breast and ovarian cancer compared to the general population. 1–5
Key Genetic Mutations Increasing Ovarian Cancer Risk
BRCA1 and BRCA2: These tumour suppressor genes help repair damaged DNA, and harmful mutations can impair this process, leading to increased cancer risk.1,2 Approximately 10–15% of ovarian cancers are due to inherited mutations in BRCA1 or BRCA2 genes.1,6 Women with BRCA1 mutations have an estimated 39–63% risk of developing ovarian cancer by age 70, while BRCA2 mutation carriers have about a 10–31% risk.1,2,4
Mutation location matters: Certain regions within the BRCA1 and BRCA2 genes are associated with higher ovarian cancer risk, showing that not all mutations confer identical risk levels. 2,5
Other Genetic Conditions: Mutations in genes associated with Lynch syndrome (e.g., MLH1, MSH2, MSH6), as well as BRIP1, RAD51C, and RAD51D, also increase ovarian cancer risk, though these account for a smaller percentage compared to BRCA mutations. 2,5
HBOC (Hereditary Breast and Ovarian Cancer Syndrome)
· This syndrome, caused mainly by BRCA1/2 mutations, is characterised by an increased risk of breast and ovarian cancers within families.5 Individuals in families with multiple ovarian or breast cancer cases have higher likelihoods of harbouring these mutations. However, mutations can also be found in individuals without significant family history due to variable penetrance and genetic background.2,5
Genetic testing is advised for women with a personal or family history of ovarian cancer, male breast cancer, pancreatic cancer, or metastatic or high-risk prostate cancer, or known BRCA-related cancers. Testing is especially recommended for women of Ashkenazi Jewish descent who have higher prevalence of founder mutations. 1,3,6
Identification of a mutation allows for tailored risk management including enhanced surveillance, prophylactic surgeries, and targeted therapies to reduce ovarian cancer incidence and mortality. 2,3,5,6
1: https://www.moffitt.org/cancers/ovarian-cancer/faqs/number-one-risk-factor-for-ovarian-cancer/
2: https://pmc.ncbi.nlm.nih.gov/articles/PMC5527889/
3: https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet
4: https://www.acog.org/womens-health/faqs/brca1-and-brca2-mutations