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

in Endocrine-Related Cancer
Authors:
Masaki Shiota Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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https://orcid.org/0000-0002-3306-4858
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Shuichi Tatarano Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

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https://orcid.org/0000-0003-4224-5084
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Toshiyuki Kamoto Department of Urology, Faculty of Medicine, Miyazaki University, Miyazaki, Japan

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Hideyasu Matsuyama Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan

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Hideki Sakai Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

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Tsukasa Igawa Department of Urology, School of Medicine, Kurume University, Kurume, Japan

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Tomomi Kamba Department of Urology, Kumamoto University, Kumamoto, Japan

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Naohiro Fujimoto Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

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Yuya Sekine Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Department of Urology, Graduate School of Medicine, Akita University, Akita, Japan

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Hiroko Kimura Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Shintaro Narita Department of Urology, Graduate School of Medicine, Akita University, Akita, Japan

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Naoki Terada Department of Urology, Faculty of Medicine, Miyazaki University, Miyazaki, Japan

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Yukihide Momozawa Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

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Shusuke Akamatsu Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Tomonori Habuchi Department of Urology, Graduate School of Medicine, Akita University, Akita, Japan

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Akira Yokomizo Department of Urology, Harasanshin Hospital, Fukuoka, Japan

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Seiji Naito Department of Urology, Harasanshin Hospital, Fukuoka, Japan

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Masatoshi Eto Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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Correspondence should be addressed to M Shiota: shiota.masaki.101@m.kyushu-u.ac.jp
DOI:
https://doi.org/10.1530/ERC-23-0044
Volume/Issue:
Volume 30: Issue 7
Article Type:
Research Article
Article ID:
e230044
Online Publication Date:
01 Jun 2023
Copyright:
© the author(s) 2023
Restricted access
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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.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2023
Article ID:
e230044
Received Date:
11 Apr 2023
Accepted Date:
20 Apr 2023
Print Publication Date:
01 Jul 2023
Online Publication Date:
01 Jun 2023
Keywords:
advanced prostate cancer; androgen-deprivation therapy; genome-wide association study; prognosis; validation

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