Abstract：
OBJECTIVE: 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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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：卵巢癌（OC）中同源重组修复（HRR）和Lynch综合征（LS）基因中种系致病变异（PV）的患病率尚不确定。
方法：一项观察性研究报告了1996年9月至2024年5月在西北基因组实验室中心测试的所有OC病例中HRR和LS基因中种系PVs的检出率。对于2021年4月至2024年5月之间测试的未选择病例，与诊断基因测序研究后乳腺癌风险的50703对照，使用比值比（OR）和95％置信区间（95％CI）报告效应大小。
结果：2934名女性接受了BRCA1/2检测，433名(14.8%)女性接受了PV检测。在多达1572名女性中测试了非BRCA1/2HRR基因的PV，检出率为PALB2=0.8%,BRIP1=1.1%，RAD51C=0.4%，RAD51D=0.4%。在940个未选定的案例中，BRIP1（OR=8.7，95％CI4.6-15.8）是第三常见的OC易感性基因，其次是RAD51C（OR=8.3，95％CI3.1-23.1），RAD51D（OR=6.5，95%CI2.1-19.7）和PALB2（OR=3.9，95%CI1.5-10.3）。在未选择的病例中未检测到LS基因中的PV。
结论：在非BRCA1/2HRR基因中，OC中的小组检测导致种系PV的检出率为2-3％，最大的贡献者是BRIP1。在未选择的OC病例中筛查LS是不必要的。
方法：一项观察性研究报告了1996年9月至2024年5月在西北基因组实验室中心测试的所有OC病例中HRR和LS基因中种系PVs的检出率。对于2021年4月至2024年5月之间测试的未选择病例，与诊断基因测序研究后乳腺癌风险的50703对照，使用比值比（OR）和95％置信区间（95％CI）报告效应大小。
结果：2934名女性接受了BRCA1/2检测，433名(14.8%)女性接受了PV检测。在多达1572名女性中测试了非BRCA1/2HRR基因的PV，检出率为PALB2=0.8%,BRIP1=1.1%，RAD51C=0.4%，RAD51D=0.4%。在940个未选定的案例中，BRIP1（OR=8.7，95％CI4.6-15.8）是第三常见的OC易感性基因，其次是RAD51C（OR=8.3，95％CI3.1-23.1），RAD51D（OR=6.5，95%CI2.1-19.7）和PALB2（OR=3.9，95%CI1.5-10.3）。在未选择的病例中未检测到LS基因中的PV。
结论：在非BRCA1/2HRR基因中，OC中的小组检测导致种系PV的检出率为2-3％，最大的贡献者是BRIP1。在未选择的OC病例中筛查LS是不必要的。
