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Observational Study
. 2024 Oct;26(10):101230.
doi: 10.1016/j.gim.2024.101230. Epub 2024 Jul 31.

Extended panel testing in ovarian cancer reveals BRIP1 as the third most important predisposition gene

Robert D Morgan  1 , George J Burghel  2 , Nicola Flaum  3 , Helene Schlecht  4 , Andrew R Clamp  3 , Jurjees Hasan  5 , Claire Mitchell  5 , Zena Salih  5 , Sarah Moon  6 , Martin Hogg  7 , Rosemary Lord  8 , Claire Forde  9 , Fiona Lalloo  9 , Emma R Woodward  9 , Emma J Crosbie  10 , Stephen S Taylor  11 , Gordon C Jayson  3 , D Gareth R Evans  12
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Free article
Observational Study

Extended panel testing in ovarian cancer reveals BRIP1 as the third most important predisposition gene

Robert D Morgan et al. Genet Med. 2024 Oct.
Free article

Abstract

Purpose: The prevalence of germline pathogenic variants (PVs) in homologous recombination repair (HRR) and Lynch syndrome (LS) genes in ovarian cancer (OC) is uncertain.

Methods: An observational study reporting the detection rate of germline PVs in HRR and LS genes in all OC cases tested in the North West Genomic Laboratory Hub between September 1996 and May 2024. Effect sizes are reported using odds ratios (ORs) and 95% confidence intervals (95% CI) for unselected cases tested between April 2021 and May 2024 versus 50,703 controls from the Breast Cancer Risk after Diagnostic Gene Sequencing study.

Results: 2934 women were tested for BRCA1/2 and 433 (14.8%) had a PV. In up to 1572 women tested for PVs in non-BRCA1/2 HRR genes, detection rates were PALB2 = 0.8%, BRIP1 = 1.1%, RAD51C = 0.4% and RAD51D = 0.4%. In 940 unselected cases, BRIP1 (OR = 8.7, 95% CI 4.6-15.8) was the third most common OC predisposition gene followed by RAD51C (OR = 8.3, 95% CI 3.1-23.1), RAD51D (OR = 6.5, 95% CI 2.1-19.7), and PALB2 (OR = 3.9, 95% CI 1.5-10.3). No PVs in LS genes were detected in unselected cases.

Conclusion: Panel testing in OC resulted in a detection rate of 2% to 3% for germline PVs in non-BRCA1/2 HRR genes, with the largest contributor being BRIP1. Screening for LS in unselected cases of OC is unnecessary.

Keywords: BRIP1; Germline variants; Homologous recombination; Lynch syndrome; Ovarian cancer.

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Conflict of interest statement

Conflict of Interest Professor Gareth Evans has received consultancy fees from AstraZeneca and Everything Genetic Ltd. Professor Gordon Jayson has received research funding from AstraZeneca. Dr Andrew Clamp has received research funding from AstraZeneca. Dr Rosemary Lord has performed advisory work for GSK. All other authors declare no conflicts of interest.

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