Genome-wide association studies in advanced prostate cancer: KYUCOG-1401-A study-Reference-Cited by-同舟云学术

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

Published:2023-04-20 Issue:7 Volume:30 Page:
ISSN:1351-0088
Container-title:Endocrine-Related Cancer
language:
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Author:

Shiota Masaki¹^ORCID,Tatarano Shuichi²^ORCID,Kamoto Toshiyuki³,Matsuyama Hideyasu⁴,Sakai Hideki⁵,Igawa Tsukasa⁶,Kamba Tomomi⁷,Fujimoto Naohiro⁸,Sekine Yuya⁹¹⁰,Kimura Hiroko¹¹,Narita Shintaro¹⁰,Terada Naoki³,Momozawa Yukihide⁹,Akamatsu Shusuke¹¹,Habuchi Tomonori¹⁰,Yokomizo Akira¹²,Naito Seiji¹²,Eto Masatoshi¹

Affiliation:

1. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

2. Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

3. Department of Urology, Faculty of Medicine, Miyazaki University, Miyazaki, Japan

4. Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, Japan

5. Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

6. Department of Urology, School of Medicine, Kurume University, Kurume, Japan

7. Department of Urology, Kumamoto University, Kumamoto, Japan

8. Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

9. Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

10. Department of Urology, Graduate School of Medicine, Akita University, Akita, Japan

11. Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

12. Department of Urology, Harasanshin Hospital, Fukuoka, Japan

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.

Publisher

Bioscientifica

Subject

Cancer Research,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism

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