Robert D. Morgan , George J. Burghel , Nicola Flaum , Helene Schlecht , Andrew R. Clamp , Jurjees Hasan , Claire Mitchell , Zena Salih , Sarah Moon , Martin Hogg , Rosemary Lord , Claire Forde , Fiona Lalloo , Emma R. Woodward , Emma J. Crosbie , Stephen S. Taylor , Gordon C. Jayson , D. Gareth R. Evans
{"title":"卵巢癌扩展面板测试显示，BRIP1 是第三个最重要的易感基因。","authors":"Robert D. Morgan , George J. Burghel , Nicola Flaum , Helene Schlecht , Andrew R. Clamp , Jurjees Hasan , Claire Mitchell , Zena Salih , Sarah Moon , Martin Hogg , Rosemary Lord , Claire Forde , Fiona Lalloo , Emma R. Woodward , Emma J. Crosbie , Stephen S. Taylor , Gordon C. Jayson , D. Gareth R. Evans","doi":"10.1016/j.gim.2024.101230","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>The prevalence of germline pathogenic variants (PVs) in homologous recombination repair (HRR) and Lynch syndrome (LS) genes in ovarian cancer (OC) is uncertain.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>2934 women were tested for <em>BRCA1/2</em> and 433 (14.8%) had a PV. In up to 1572 women tested for PVs in non-<em>BRCA1/2</em> HRR genes, detection rates were <em>PALB2</em> = 0.8%, <em>BRIP1</em> = 1.1%, <em>RAD51C</em> = 0.4% and <em>RAD51D</em> = 0.4%. In 940 unselected cases, <em>BRIP1</em> (OR = 8.7, 95% CI 4.6-15.8) was the third most common OC predisposition gene followed by <em>RAD51C</em> (OR = 8.3, 95% CI 3.1-23.1), <em>RAD51D</em> (OR = 6.5, 95% CI 2.1-19.7), and <em>PALB2</em> (OR = 3.9, 95% CI 1.5-10.3). No PVs in LS genes were detected in unselected cases.</p></div><div><h3>Conclusion</h3><p>Panel testing in OC resulted in a detection rate of 2% to 3% for germline PVs in non-<em>BRCA1/2</em> HRR genes, with the largest contributor being <em>BRIP1</em>. Screening for LS in unselected cases of OC is unnecessary.</p></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":"26 10","pages":"Article 101230"},"PeriodicalIF":6.6000,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1098360024001643/pdfft?md5=daf4f1124905a3cde941ff3691384c99&pid=1-s2.0-S1098360024001643-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Extended panel testing in ovarian cancer reveals BRIP1 as the third most important predisposition gene\",\"authors\":\"Robert D. Morgan , George J. Burghel , Nicola Flaum , Helene Schlecht , Andrew R. Clamp , Jurjees Hasan , Claire Mitchell , Zena Salih , Sarah Moon , Martin Hogg , Rosemary Lord , Claire Forde , Fiona Lalloo , Emma R. Woodward , Emma J. Crosbie , Stephen S. Taylor , Gordon C. Jayson , D. Gareth R. Evans\",\"doi\":\"10.1016/j.gim.2024.101230\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><p>The prevalence of germline pathogenic variants (PVs) in homologous recombination repair (HRR) and Lynch syndrome (LS) genes in ovarian cancer (OC) is uncertain.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>2934 women were tested for <em>BRCA1/2</em> and 433 (14.8%) had a PV. In up to 1572 women tested for PVs in non-<em>BRCA1/2</em> HRR genes, detection rates were <em>PALB2</em> = 0.8%, <em>BRIP1</em> = 1.1%, <em>RAD51C</em> = 0.4% and <em>RAD51D</em> = 0.4%. In 940 unselected cases, <em>BRIP1</em> (OR = 8.7, 95% CI 4.6-15.8) was the third most common OC predisposition gene followed by <em>RAD51C</em> (OR = 8.3, 95% CI 3.1-23.1), <em>RAD51D</em> (OR = 6.5, 95% CI 2.1-19.7), and <em>PALB2</em> (OR = 3.9, 95% CI 1.5-10.3). No PVs in LS genes were detected in unselected cases.</p></div><div><h3>Conclusion</h3><p>Panel testing in OC resulted in a detection rate of 2% to 3% for germline PVs in non-<em>BRCA1/2</em> HRR genes, with the largest contributor being <em>BRIP1</em>. Screening for LS in unselected cases of OC is unnecessary.</p></div>\",\"PeriodicalId\":12717,\"journal\":{\"name\":\"Genetics in Medicine\",\"volume\":\"26 10\",\"pages\":\"Article 101230\"},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2024-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1098360024001643/pdfft?md5=daf4f1124905a3cde941ff3691384c99&pid=1-s2.0-S1098360024001643-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetics in Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1098360024001643\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetics in Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1098360024001643","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
目的：卵巢癌（OC）中同源重组修复（HRR）和林奇综合征（LS）基因种系致病变异（PVs）的发生率尚不确定：一项观察性研究，报告 1996 年 9 月至 2024 年 5 月期间西北基因组实验室中心检测的所有卵巢癌病例中 HRR 和 LS 基因种系 PV 的检出率。结果：2934 名妇女接受了 BRCA1/2 检测，其中 433 人（14.8%）有 PV。在接受非 BRCA1/2 HRR 基因 PV 检测的多达 1572 名妇女中，检出率分别为 PALB2=0.8%、BRIP1=1.1%、RAD51C=0.4% 和 RAD51D=0.4%。在 940 个未入选病例中，BRIP1（OR=8.7，95% CI 4.6-15.8）是第三常见的 OC 易感基因，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）。未入选病例中未检测到 LS 基因的 PV：结论：在OC中进行基因组检测，非BRCA1/2 HRR基因的种系PV检出率为2%-3%，其中最大的贡献基因是BRIP1。没有必要对未经筛选的 OC 病例进行 LS 筛查。
Extended panel testing in ovarian cancer reveals BRIP1 as the third most important predisposition gene
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.
期刊介绍：
Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health.
GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.
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