Genome-wide association studies in advanced prostate cancer: KYUCOG-1401-A study.

IF 4.1 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine-related cancer Pub Date : 2023-07-01 DOI:10.1530/ERC-23-0044

Masaki Shiota, Shuichi Tatarano, Toshiyuki Kamoto, Hideyasu Matsuyama, Hideki Sakai, Tsukasa Igawa, Tomomi Kamba, Naohiro Fujimoto, Yuya Sekine, Hiroko Kimura, Shintaro Narita, Naoki Terada, Yukihide Momozawa, Shusuke Akamatsu, Tomonori Habuchi, Akira Yokomizo, Seiji Naito, Masatoshi Eto

{"title":"Genome-wide association studies in advanced prostate cancer: KYUCOG-1401-A study.","authors":"Masaki Shiota, Shuichi Tatarano, Toshiyuki Kamoto, Hideyasu Matsuyama, Hideki Sakai, Tsukasa Igawa, Tomomi Kamba, Naohiro Fujimoto, Yuya Sekine, Hiroko Kimura, Shintaro Narita, Naoki Terada, Yukihide Momozawa, Shusuke Akamatsu, Tomonori Habuchi, Akira Yokomizo, Seiji Naito, Masatoshi Eto","doi":"10.1530/ERC-23-0044","DOIUrl":null,"url":null,"abstract":"<p><p>Androgen-deprivation therapy (ADT) has been widely used for the treatment of advanced prostate cancer. However, prognosis and adverse events (AEs) vary among patients. This study aimed to identify genetic markers able to predict the outcome of ADT. Japanese patients treated with primary ADT for advanced prostate cancer in the KYUCOG-1401 trial were enrolled as a development set. A distinct population of advanced prostate cancer cases treated with ADT was included as a validation set. Single-nucleotide polymorphisms (SNPs) associated with radiographic progression-free survival (rPFS) at 1 year and AEs including de novo diabetes mellitus (DM), arthralgia, and de novo dyslipidemia were identified in the development set by a genome-wide association study (GWAS). The SNPs associated with rPFS in the development study were then genotyped in the validation set. GWAS followed by validation identified SNPs (rs76237622 in PRR27 and rs117573572 in MTAP) that were associated with overall survival (OS) in ADT. A genetic prognostic model using these SNPs showed excellent predictive efficacy for PFS and OS in ADT. In addition, GWAS showed that several SNPs were associated with de novo DM, arthralgia, and de novo dyslipidemia in ADT. This study identified novel multiple SNPs that correlated with outcomes in ADT. Future studies on correlations affecting the therapeutic efficacy of ADT-based combination therapies would make a valuable contribution to the development of personalized medicine.</p>","PeriodicalId":11654,"journal":{"name":"Endocrine-related cancer","volume":"30 7","pages":""},"PeriodicalIF":4.1000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine-related cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1530/ERC-23-0044","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Androgen-deprivation therapy (ADT) has been widely used for the treatment of advanced prostate cancer. However, prognosis and adverse events (AEs) vary among patients. This study aimed to identify genetic markers able to predict the outcome of ADT. Japanese patients treated with primary ADT for advanced prostate cancer in the KYUCOG-1401 trial were enrolled as a development set. A distinct population of advanced prostate cancer cases treated with ADT was included as a validation set. Single-nucleotide polymorphisms (SNPs) associated with radiographic progression-free survival (rPFS) at 1 year and AEs including de novo diabetes mellitus (DM), arthralgia, and de novo dyslipidemia were identified in the development set by a genome-wide association study (GWAS). The SNPs associated with rPFS in the development study were then genotyped in the validation set. GWAS followed by validation identified SNPs (rs76237622 in PRR27 and rs117573572 in MTAP) that were associated with overall survival (OS) in ADT. A genetic prognostic model using these SNPs showed excellent predictive efficacy for PFS and OS in ADT. In addition, GWAS showed that several SNPs were associated with de novo DM, arthralgia, and de novo dyslipidemia in ADT. This study identified novel multiple SNPs that correlated with outcomes in ADT. Future studies on correlations affecting the therapeutic efficacy of ADT-based combination therapies would make a valuable contribution to the development of personalized medicine.

查看原文本刊更多论文

晚期前列腺癌的全基因组关联研究:KYUCOG-1401-A研究

雄激素剥夺疗法(ADT)已广泛应用于晚期前列腺癌的治疗。然而，患者的预后和不良事件(ae)各不相同。本研究旨在鉴定能够预测ADT预后的遗传标记。KYUCOG-1401试验中接受原发性ADT治疗晚期前列腺癌的日本患者被纳入研究。一组接受ADT治疗的晚期前列腺癌病例被纳入验证组。在一项全基因组关联研究(GWAS)中，发现了与1年放射学无进展生存期(rPFS)和ae相关的单核苷酸多态性(snp)，包括新发糖尿病(DM)、关节痛和新发血脂异常。发育研究中与rPFS相关的snp随后在验证集中进行基因分型。GWAS验证后发现了与ADT总生存期(OS)相关的snp (PRR27中的rs76237622和MTAP中的rs117573572)。使用这些snp的遗传预后模型对ADT的PFS和OS具有良好的预测效果。此外，GWAS显示几个snp与ADT患者的新发DM、关节痛和新发血脂异常有关。本研究发现了与ADT预后相关的新的多个snp。未来对影响以adt为基础的联合治疗疗效的相关性的研究将为个性化医疗的发展做出宝贵的贡献。

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

Endocrine-related cancer 医学-内分泌学与代谢

CiteScore

7.80

自引率

2.60%

发文量

138

审稿时长

6-12 weeks

期刊介绍： Endocrine-Related Cancer is an official flagship journal of the Society for Endocrinology and is endorsed by the European Society of Endocrinology, the United Kingdom and Ireland Neuroendocrine Society, and the Japanese Hormones and Cancer Society. Endocrine-Related Cancer provides a unique international forum for the publication of high quality original articles describing novel, cutting edge basic laboratory, translational and clinical investigations of human health and disease focusing on endocrine neoplasias and hormone-dependent cancers; and for the publication of authoritative review articles in these topics. Endocrine neoplasias include adrenal cortex, breast, multiple endocrine neoplasia, neuroendocrine tumours, ovary, prostate, paraganglioma, parathyroid, pheochromocytoma pituitary, testes, thyroid and hormone-dependent cancers. Neoplasias affecting metabolism and energy production such as bladder, bone, kidney, lung, and head and neck, are also considered.