卵巢癌的扩展面板检测显示 BRIP1 为第三大重要易患病基因。

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

机构信息

The Christie NHS Foundation Trust, Manchester, United Kingdom; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.

Manchester Centre for Genomic Medicine, North West Genomic Laboratory Hub, Manchester, United Kingdom; Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.

出版信息

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

DOI:10.1016/j.gim.2024.101230

PMID:39096152

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.

摘要

目的

同源重组修复（HRR）和林奇综合征（LS）基因种系致病性变异（PVs）在卵巢癌（OC）中的流行情况尚不确定。

方法

本观察性研究报告了 1996 年 9 月至 2024 年 5 月期间在西北基因组实验室中心检测的所有 OC 病例中 HRR 和 LS 基因种系 PV 的检出率。在 2021 年 4 月至 2024 年 5 月期间对未选择的病例进行检测的效应大小使用比值比（ORs）和 95%置信区间（95%CI）报告，对照组来自诊断基因测序后乳腺癌风险研究的 50703 例。

结果

对 2934 名女性进行了 BRCA1/2 检测，其中 433 名（14.8%）存在 PV。在多达 1572 名女性中检测了非 BRCA1/2 HRR 基因的种系 PV，PALB2 的检出率为 0.8%，BRIP1 为 1.1%，RAD51C 为 0.4%，RAD51D 为 0.4%。在 940 例未选择的病例中，BRIP1（OR=8.7，95%CI 4.6-15.8）是 OC 易感性的第三大常见基因，其次是 RAD51C（OR=8.3，95%CI 3.1-23.1）、RAD51D（OR=6.5，95%CI 2.1-19.7）和 PALB2（OR=3.9，95%CI 1.5-10.3）。在未选择的病例中未发现 LS 基因的种系 PV。