Ovarian cancer: identifying and managing familial and genetic risk

Context

Familial ovarian cancer affects people born with female reproductive organs (ovaries, fallopian tubes and/or a uterus). Although in this guideline, the term ovarian cancer is used throughout, there is now evidence that most high-grade serous cancers (the most common type of ovarian cancer) arise from the distal fallopian tube from a precursor lesion referred to as serous tubal intraepithelial carcinoma (STIC).

In the UK, between 340,000 and 440,000 women have a pathogenic variant associated with an increased risk of ovarian cancer. This includes pathogenic variants in BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, MLH1, MSH2 and MSH6 genes. It is estimated that 15% to 20% of those with high-grade epithelial ovarian cancer also carry a pathogenic variant associated with increased risk of ovarian cancer.

Most of the people who carry a pathogenic variant for ovarian cancer do not have a family history suggestive of a genetic risk. This means many people have not sought testing for high-risk ovarian cancer pathogenic variants. Current best estimates are that only 3% of people with a pathogenic variant know that they are carriers. This proportion will increase with improved availability of genetic testing.

Most women and people born with female reproductive organs who carry a pathogenic variant will not develop ovarian cancer. This guideline recommends how to assess the risk of having a pathogenic variant and the risk of developing ovarian cancer, what risk-reducing interventions should or should not be offered, and what information and support should be given.

The guideline does not cover risk management and decision-making support for people born with male reproductive organs who have, or are at risk of having, a pathogenic variant associated with ovarian cancer. This is because they are not at risk of developing ovarian cancer, and the decisions that they would have to make are different and outside the scope of this guideline.