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High detection rate from genetic testing in BRCA-negative women with familial epithelial ovarian cancer
Flaum, N. Crosbie, E. J. Edmondson, R. Woodward, E. R. Lalloo, F. Smith, M. J. Schlecht, H. Evans, D Gareth R
Flaum, N.
Crosbie, E. J.
Edmondson, R.
Woodward, E. R.
Lalloo, F.
Smith, M. J.
Schlecht, H.
Evans, D Gareth R
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Abstract
Purpose: 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.
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Date
2022
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Article
Citation
Flaum 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.