Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer.

IF 5.7 2区医学 Q1 Medicine

Cancer Science Pub Date : 2024-10-10 DOI:10.1111/cas.16367

Maiko Miwa, Masakazu Kitagawa, Yuka Asami, Mayumi Kobayashi-Kato, Takafumi Watanabe, Aiko Ogasawara, Kengo Hiranuma, Hisamori Kato, Motonobu Saito, Yohei Miyagi, Tomoyasu Kato, Hiroshi Yoshida, Yukihide Momozawa, Takashi Kohno, Kouya Shiraishi, Kosei Hasegawa

{"title":"Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer.","authors":"Maiko Miwa, Masakazu Kitagawa, Yuka Asami, Mayumi Kobayashi-Kato, Takafumi Watanabe, Aiko Ogasawara, Kengo Hiranuma, Hisamori Kato, Motonobu Saito, Yohei Miyagi, Tomoyasu Kato, Hiroshi Yoshida, Yukihide Momozawa, Takashi Kohno, Kouya Shiraishi, Kosei Hasegawa","doi":"10.1111/cas.16367","DOIUrl":null,"url":null,"abstract":"<p><p>Germline pathogenic variants (PVs) are pivotal in gynecological oncology. We focused on the prevalence, clinicopathological features, and survival impact of homologous recombination repair (HRR) PVs in patients with epithelial ovarian cancer (EOC). This was a multicenter retrospective cohort study, and 1248 patients with EOC were registered. Eligible patients (n = 1112) underwent germline DNA analysis for 26 cancer predisposition genes, including nine HRR-related genes, such as BRCA1/2, BRIP1, PALB2, RAD51C/D, and ATM. The associations between clinicopathological factors and HRR-related PVs were examined. Kaplan-Meier and Cox regression analyses were conducted. Among 1091 analyzed patients, 153 (14.0%) carried PVs and 140 (12.8%) were HRR-related. HRR-PV-positive status significantly correlated with serous carcinoma (22.9% vs. 4.8%, P < 0.0001) and advanced disease (18.5% vs. 5.9%, P < 0.0001). The HRR-PV-positive group exhibited higher prevalence of personal breast (12.9%) and familial breast/ovarian (29.2%) cancer history. HRR status independently improved overall survival in stage III/IV disease (P = 0.04) but not progression-free survival. HRR-related germline PVs exhibit distinct clinicopathological features with survival implications. Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000-2019), the limited use of bevacizumab and poly (ADP-ribose) polymerase inhibitors as maintenance therapy should be recognized.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cas.16367","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Germline pathogenic variants (PVs) are pivotal in gynecological oncology. We focused on the prevalence, clinicopathological features, and survival impact of homologous recombination repair (HRR) PVs in patients with epithelial ovarian cancer (EOC). This was a multicenter retrospective cohort study, and 1248 patients with EOC were registered. Eligible patients (n = 1112) underwent germline DNA analysis for 26 cancer predisposition genes, including nine HRR-related genes, such as BRCA1/2, BRIP1, PALB2, RAD51C/D, and ATM. The associations between clinicopathological factors and HRR-related PVs were examined. Kaplan-Meier and Cox regression analyses were conducted. Among 1091 analyzed patients, 153 (14.0%) carried PVs and 140 (12.8%) were HRR-related. HRR-PV-positive status significantly correlated with serous carcinoma (22.9% vs. 4.8%, P < 0.0001) and advanced disease (18.5% vs. 5.9%, P < 0.0001). The HRR-PV-positive group exhibited higher prevalence of personal breast (12.9%) and familial breast/ovarian (29.2%) cancer history. HRR status independently improved overall survival in stage III/IV disease (P = 0.04) but not progression-free survival. HRR-related germline PVs exhibit distinct clinicopathological features with survival implications. Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000-2019), the limited use of bevacizumab and poly (ADP-ribose) polymerase inhibitors as maintenance therapy should be recognized.

查看原文本刊更多论文

卵巢癌中同源重组修复基因种系致病变异的发生率和结果。

种系致病变异（PVs）在妇科肿瘤学中至关重要。我们重点研究了上皮性卵巢癌（EOC）患者中同源重组修复（HRR）PVs的发生率、临床病理特征和对生存的影响。这是一项多中心回顾性队列研究，共登记了 1248 例 EOC 患者。符合条件的患者（n = 1112）接受了26个癌症易感基因的种系DNA分析，其中包括9个与HRR相关的基因，如BRCA1/2、BRIP1、PALB2、RAD51C/D和ATM。研究还探讨了临床病理因素与 HRR 相关 PV 之间的关系。研究人员进行了 Kaplan-Meier 和 Cox 回归分析。在分析的1091例患者中，153例（14.0%）携带PV，140例（12.8%）与HRR相关。HRR-PV阳性状态与浆液性癌明显相关（22.9% vs. 4.8%，P

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer Science ONCOLOGY-

CiteScore

9.90

自引率

3.50%

发文量

406

审稿时长

17 weeks

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.