Probability of detecting germline BRCA1/2 pathogenic variants in histological subtypes of ovarian carcinoma. A meta-analysis
Witjes, Vera M.; van Bommel, Majke H.D.; Ligtenberg, Marjolijn J.L.; Vos, Janet R.; Mourits, Marian J.E.; Ausems, Margreet G.E.M.; de Hullu, Joanne A.; Bosse, Tjalling; Hoogerbrugge, Nicoline
(2022) Gynecologic Oncology, volume 164, issue 1, pp. 221 - 230
(Article)
Abstract
Background: Histology restricted genetic predisposition testing of ovarian carcinoma patients is a topic of debate as the prevalence of BRCA1/2 pathogenic variants (PVs) in various histological subtypes is ambiguous. Our primary aim was to investigate the proportion of germline BRCA1/2 PVs per histological subtype. Additionally, we evaluated (i) proportion of
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somatic BRCA1/2 PVs and (ii) proportion of germline PVs in other ovarian carcinoma risk genes. Methods: PubMed, EMBASE and Web of Science were systematically searched and we included all studies reporting germline BRCA1/2 PVs per histological subtype. Pooled proportions were calculated using a random-effects meta-analysis model. Subsets of studies were used for secondary analyses. Results: Twenty-eight studies were identified. The overall estimated proportion of germline BRCA1/2 PVs was 16.8% (95% CI 14.6 to 19.2). Presence differed substantially among patients with varying histological subtypes of OC; proportions being highest in high-grade serous (22.2%, 95% CI 19.6 to 25.0) and lowest in clear cell (3.0%, 95% CI 1.6 to 5.6) and mucinous (2.5%, 95% CI 0.6 to 9.6) carcinomas. Somatic BRCA1/2 PVs were present with total estimated proportion of 6.0% (95% CI 5.0 to 7.3), based on a smaller subset of studies. Germline PVs in BRIP1, RAD51C, RAD51D, PALB2, and ATM were present in approximately 3%, based on a subset of nine studies. Conclusion: Germline BRCA1/2 PVs are most frequently identified in high-grade serous ovarian carcinoma patients, but are also detected in patients having ovarian carcinomas of other histological subtypes. Limiting genetic predisposition testing to high-grade serous ovarian carcinoma patients will likely be insufficient to identify all patients with a germline PV.
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Keywords: BRCA, Epithelial ovarian cancer, Genetic testing, Histology, Probability, Genetic Testing, Humans, Genetic Predisposition to Disease/genetics, Ovarian Neoplasms/genetics, BRCA2 Protein/genetics, Germ-Line Mutation, Female, BRCA1 Protein/genetics, Obstetrics and Gynaecology, Oncology, Research Support, Non-U.S. Gov't, Meta-Analysis, Journal Article
ISSN: 0090-8258
Publisher: Academic Press Inc.
Note: Funding Information: This work was supported by a grant from the Dutch Cancer Society ( KUN2019–12732 ). Publisher Copyright: © 2021 The Authors Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
(Peer reviewed)