High detection rate from genetic testing in BRCA-negative women with familial epithelial ovarian cancer
Crosbie, E. J.
Woodward, E. R.
Smith, M. J.
Evans, D Gareth R
AffiliationDivision of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, United Kingdom
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AbstractPurpose: Epithelial ovarian cancer (EOC) is associated with pathogenic variants (PVs) in homologous recombination and/or mismatch repair genes. We aimed to review the testing of women with familial EOC at our center. Methods: Women with familial EOC (≥2 EOC in family, including index case) referred to our center between 1993 and 2021 were included. Genetic testing (BRCA/Lynch syndrome screening, exome sequencing, panel testing, 100,000 Genome Project, and NIHR BioResource genome sequencing) and clinical demographic, diagnosis, and survival data were reviewed. Results: Of 277, 128 (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 was BRIP1 (5.9%). The non-BRCA detection rate was significantly higher in families with 2 affected members with EOC only (22.4%) than the families with ≥3 (11.1%) affected members (odds ratio = 9.9, 95% CI = 1.6-105.2, P = .0075). Overall, 112 different PVs in 12 homologous recombination/mismatch repair genes were detected in 150 of 277 (54.2%) unrelated women. Conclusion: This is the largest report of women with familial EOC undergoing wider testing to date. One-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 optimize their treatment and prevention of disease in family members.
CitationFlaum N, Crosbie EJ, Edmondson R, Woodward ER, Lalloo F, Smith MJ, et al. High detection rate from genetic testing in BRCA-negative women with familial epithelial ovarian cancer. Genetics in medicine : official journal of the American College of Medical Genetics. 2022 Sep 28. PubMed PMID: 36169650. Epub 2022/09/29. eng.
JournalGenetics in Medicine
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