Genetic testing and ovarian cancer- what do we need to know?

Jonathon is a 40 yr old man newly registered at your surgery. He attends for review of his IBS and medication. As part of the consultation you enquire about family history of cancer. ‘Oh nothing relevant’, he says. On further clarification he reports that his sister had ovarian cancer. Understandably, given his lack of the requisite anatomy, he does not think that this affects his risk profile.

Is he correct?

Ovarian cancer is the sixth most common cancer affecting women in the UK, with  between 5-15% of cases linked to an inherited genetic mutation, such as BRCA1, BRCA2 and Lynch syndrome (Cancer Research UK). According to NICE, current estimates suggest that only 3% of people with a pathogenic variant (inherited genetic mutation linked to increased risk of cancer) for ovarian cancer are aware that they are carriers. 

Why is it important to identify those with pathogenic variants early? Having the BRCA1 mutation significantly increases the risk of ovarian cancer from 2% in the general population to 40-60%  (Ovarian Cancer Action). Detection of the mutation in people without cancer allows discussion of risk reduction options such as surgery (bilateral salpingo-oophorectomy), increased surveillance, and medication. It can also inform family planning decisions; for example some may wish to bring forward family plans prior to risk reduction surgery, or to explore the possibility of pre-implantation genetic testing due to the risk of passing the mutation to children. Many of these pathogenic variants are also associated with an increased risk of other types of cancer, for example BRCA2 is linked to breast, prostate, and pancreatic cancer. 

So what is the role of primary care in genetic screening? The new NICE guidance ‘Ovarian cancer: identifying and managing familial and genetic risk’ NG241 is the first to focus specifically on familial ovarian cancer ( there is some overlap with familial breast cancer guidelines CG164). Importantly, eligibility is expanded to those with a single first degree relative with ovarian cancer. It advises that we should refer people over the age of 18y (of any gender) for genetic counselling and possible testing if ANY of the following apply:

• They have a first degree relative of any age with ovarian cancer 
• They have a maternal or paternal second degree relative with ovarian cancer (even if there is an unaffected relative in between e.g. grandmother with ovarian cancer, mother cancer negative but not genetically tested)
• They meet the criteria for genetic testing
• From an at risk population i.e. with at least one grandparent from any of these populations: Ashkenazi Jewish, Sephardi Jewish, Greenlander 
• They have been identified as at risk via cascade testing (i.e. testing of other family members)
• Diagnosis of non-epithelial ovarian cancer, but have not been offered previous mainstream genetic testing 

How does this relate to Jonathon? Much to his surprise he is eligible for referral to genetic services based on having one first degree relative with ovarian cancer. Although he cannot personally contract ovarian cancer, genetic testing could inform his risk of other cancers, and the risk of passing a pathogenic variant to any children. 

 In summary, genetic testing is something we and our patients will be increasingly navigating. It can be a complex and emotive topic which needs to be sensitively approached, particularly if unexpected. Useful sources of support and patient information include the NHS website and Ovarian Cancer Action.