Up to 20 per cent of women diagnosed with ovarian cancer will have a history of ovarian cancer and breast cancer in their family. Family history is the most significant risk factor associated with developing ovarian cancer after increasing age. Risk can be conferred via the maternal and paternal line.
Mutations in the BRCA1 and BRCA2 genes are most commonly associated with ovarian cancer, as many as 15 per cent of women diagnosed carry a mutation in one of these genes.
A BRCA1 or BRCA2 mutation significantly increases an individual's lifetime risk of developing both ovarian and breast cancer. The lifetime risk of developing ovarian cancer in the general population is two per cent. This increases to between 15 and 45 per cent in individuals who carry a mutation in either of the BRCA1 or BRCA2 gene.
Other gene mutations linked to ovarian cancer include:
- RAD51C and RAD51D
- STK11 (Peutz-Jeghers syndrome)
- DNA mismatch repair genes which are those linked to Lynch syndrome (also known as hereditary non-polyposis colorectal cancer or HNPCC). HNPCC gene mutations mainly predispose individuals to colorectal and endometrial cancer, but also ovarian cancer.
A proportion of familial cases are currently unexplained but may be due to polygenic inheritance (cumulative effect of a number of genes).
Genetic screening and surveillance
Currently, there is no convincing data that surveillance using CA125 and/or pelvic ultrasound reduces mortality in women at high risk and it is not recommended for routine use. Read more about the UKFOCCS study.
GPs should make women aware of symptoms of ovarian cancer, and explain to them that the benefits of surveillance for ovarian cancer are unproven.
Risk-reducing options for women with a BRCA1 or BRCA2 mutation are limited.
Bilateral salpingo-oophorectomy (BSO) once the woman has completed her family is recommended. This will greatly reduce but not eliminate the risk of developing ovarian cancer and will also reduce the risk of breast cancer.
The exact timing of BSO, and desire to undergo such an invasive procedure, varies from one person to the next and requires a detailed discussion with a gynaecological oncologist who has expertise in preventative surgery. The PROTECTOR study is looking at the timing and nature of prophylactic surgery.
The impact of BSO is significant and women are likely to require significant support from their primary care and specialist teams. Women who have undergone BSO will immediately enter into surgically induced menopause, which will be both physically and emotionally demanding.
Women with a BRCA mutation are likely to be eligible for annual breast screening.
Women who are concerned about their genetic risk of ovarian cancer or who are considering risk reducing options can contact our support line for confidential support and information.
Establishing a family history: key questions
With these four questions it should be possible to make a rapid assessment and determine whether a more detailed investigation is required.
- Has anyone on either side of your family had ovarian and/or breast cancer?
It's crucial you consider the paternal side as well as the maternal side and actively seek this information out.
All the main cancer susceptibility genes can be passed on by either sex, but because men rarely get breast cancer the family history can appear more distant on the male side.
- Has anyone been diagnosed with breast cancer under 50 years and/or ovarian cancer at any age?
Ovarian cancer and breast cancer often develops under the age of 50 years in individuals who carry a mutation in either the BRCA1 or BRCA2 gene.
- How big is your family? How many men vs women in the family?
In small families or families with a larger proportion of men it's likely to be more difficult to establish a family history.
- Is there any Ashkenazi Jewish ancestry (where appropriate)?
BRCA1 and BRCA2 mutations are 10 times more common in individuals of Ashkenazi Jewish descent so it's important to ask about this where appropriate.
Genetic testing in women with an ovarian cancer diagnosis
NHS England guidance [PDF] advises that women in the UK diagnosed with non-mucinous ovarian cancer should be offered BRCA1 and BRCA2 mutation screening irrespective of their family history. This is because their diagnosis automatically places them above the significant risk threshold for genetic testing. Identification of a mutation has significant implications for the individual and her wider family including:
- Treatment options
Women with ovarian cancer who have a BRCA mutation might be eligible for treatment with a class of drugs known as PARP inhibitors.
- Breast cancer risk
Women have an increased risk of developing breast cancer. They may wish to discuss options including prophylactic mastectomy or frequency of breast screening.
- Impact on family
Family members will need to decide if they too wish to undergo mutation screening. They will need to and consider the potential implications of a positive screening result on their personal risk of developing ovarian and breast cancer, and the risk-reducing strategies available to them. If a woman with a family history of ovarian or breast cancer is diagnosed, she may need GP support in identifying or telling other family members at risk.
- In cases where a patient presents with concerns of hereditary ovarian cancer a first- and second-degree family history should be taken to assess individual risk.
- If an individual is considered 'at risk' they should be referred to their local clinical genetics service for further assessment. If you're unsure if your patient is at risk contact your local genetics centre for advice before making a referral.
- Men are often offered testing in the pre-symptomatic setting, for example if a man comes from a family with a known gene mutation and is worried about whether his daughters may be at risk.
- If a women has a non-mucinous type of ovarian cancer (the commonest type) then her specialist centre may offer BRCA1/BRCA2 testing, even if she did not have any other significant family history.
- Men are sometimes offered diagnostic testing if they are affected with male breast cancer, early onset pancreatic or prostate cancer (all associated with BRCA2 mutations).