Abstract
Purpose: Epithelial ovarian cancer (EOC) is associated with pathogenic variants (PVs) in homologous recombination (HR) and mismatch repair (MMR) genes. We aimed to review testing of women with familial EOC at our centre.
Methods: Women with familial EOC (≥two EOC in family including index case) referred to our centre between 1993 and 2021 were included. Genetic testing (BRCA/Lynch screening, exome sequencing, panel testing, 100,000 Genome Project and NIHR BioResource genome sequencing) and clinical demographic, diagnosis and survival data were reviewed.
Results: 128/277 (46.2%) women were BRCA heterozygotes (BRCA1- 89, BRCA2-39). The detection rate in BRCA-negative women was 21.8%; the most commonly affected gene BRIP1 (5.9%). The non-BRCA detection rate was significantly higher in families with two affected members with EOC only (22.4%), compared with families with ≥three (11.1%) (OR 9.9, 95% CI 1.6-105.2, P=0.0075). Overall 112 different PVs from 12 HR/MMR genes were detected from 150/277 (54.2%) unrelated women.
Conclusion: This is the largest report of women with familial EOC undergoing wider testing to date. A fifth of BRCA-negative women were heterozygous for a PV in a potentially actionable gene. Wider genetic testing of women with familial EOC is essential to optimise their treatment and prevention of disease in family members.
Methods: Women with familial EOC (≥two EOC in family including index case) referred to our centre between 1993 and 2021 were included. Genetic testing (BRCA/Lynch screening, exome sequencing, panel testing, 100,000 Genome Project and NIHR BioResource genome sequencing) and clinical demographic, diagnosis and survival data were reviewed.
Results: 128/277 (46.2%) women were BRCA heterozygotes (BRCA1- 89, BRCA2-39). The detection rate in BRCA-negative women was 21.8%; the most commonly affected gene BRIP1 (5.9%). The non-BRCA detection rate was significantly higher in families with two affected members with EOC only (22.4%), compared with families with ≥three (11.1%) (OR 9.9, 95% CI 1.6-105.2, P=0.0075). Overall 112 different PVs from 12 HR/MMR genes were detected from 150/277 (54.2%) unrelated women.
Conclusion: This is the largest report of women with familial EOC undergoing wider testing to date. A fifth of BRCA-negative women were heterozygous for a PV in a potentially actionable gene. Wider genetic testing of women with familial EOC is essential to optimise their treatment and prevention of disease in family members.
| Original language | English |
|---|---|
| Journal | Genetics in Medicine |
| Publication status | Accepted/In press - 23 Aug 2022 |
