2289 genetic polymorphisms of cyp17a1 may predict early progression after primary androgen deprivation therapy in japanese men with prostate cancer

You have accessJournal of UrologyProstate Cancer: Markers1 Apr 20112289 GENETIC POLYMORPHISMS OF CYP17A1 MAY PREDICT EARLY PROGRESSION AFTER PRIMARY ANDROGEN DEPRIVATION THERAPY IN JAPANESE MEN WITH PROSTATE CANCER Masashi Nakayama, Takeshi Yamada, Tomohito Shimizu, Shinpei Nonen, Kensaku Nishimura, Kazuo Nishimura, Tsuneo Hara, Go Tanigawa, Toshiaki Yoshioka, Koji Hatano, Yasutomo Nakai, Hitoshi Takayama, Yasushi Fujio, Junichi Azuma, Akihiko Okuyama, and Norio Nonomura Masashi NakayamaMasashi Nakayama Osaka-city, Osaka, Japan More articles by this author , Takeshi YamadaTakeshi Yamada Suita, Osaka, Japan More articles by this author , Tomohito ShimizuTomohito Shimizu Suita, Osaka, Japan More articles by this author , Shinpei NonenShinpei Nonen Suita, Osaka, Japan More articles by this author , Kensaku NishimuraKensaku Nishimura Sakai, Osaka, Japan More articles by this author , Kazuo NishimuraKazuo Nishimura Osaka-city, Osaka, Japan More articles by this author , Tsuneo HaraTsuneo Hara Ikeda, Osaka, Japan More articles by this author , Go TanigawaGo Tanigawa Osaka-city, Osaka, Japan More articles by this author , Toshiaki YoshiokaToshiaki Yoshioka Osaka-city, Osaka, Japan More articles by this author , Koji HatanoKoji Hatano Suita, Osaka, Japan More articles by this author , Yasutomo NakaiYasutomo Nakai Suita, Osaka, Japan More articles by this author , Hitoshi TakayamaHitoshi Takayama Suita, Osaka, Japan More articles by this author , Yasushi FujioYasushi Fujio Suita, Osaka, Japan More articles by this author , Junichi AzumaJunichi Azuma Suita, Osaka, Japan More articles by this author , Akihiko OkuyamaAkihiko Okuyama Osaka-city, Osaka, Japan More articles by this author , and Norio NonomuraNorio Nonomura Suita, Osaka, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2534AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The androgen deprivation therapy with LH-RH analogues and/or anti-androgen is the standard therapy for advanced prostate cancer. However, there is a large individual difference in the efficacy of the therapy. It is difficult to predict the duration of response to the hormonal therapy. In this study, we have examined whether genetic polymorphic variation can explain the sensitivity to hormonal therapy in Japanese patients. METHODS Two hundred fourteen patients with prostate cancer, primary treated with androgen deprivation therapy, were enrolled into this study. The median observation period from diagnosis to data collection was 43 months. We divided the subjects into three groups (I–III); Group I, ninety five patients who progressed to CRPC earlier than 43 months (high risk patients): Group II, eighty five patients who remained stable disease even after 43 months (low risk patients): Group III, thirty four patients who exhibited stable disease condition with their observation less than 43 months (short-period observation). We excluded the data of Group III from the data set, and compared the association of genotypes with the efficacy to androgen deprivation therapy in Groups I and II (high risk and low risk populations). We have selected 22 single nucleotide polymorphisms (SNPs) from 8 genes involved in androgen synthesis and metabolism that are CYP17A1, HSD3B1, SRD5A1, SRD5A2, HSD17B3, CYP1B1, CYP 11A, and CYP24A which is involved in metabolism of activated Vitamin D. The SNPs were assayed by primer extension method. Logistic regression method, with adjustments for age, clinical disease stage and Gleason score at diagnosis, was applied for the analysis. RESULTS The median observation period from diagnosis to data collection was 43 months. We observed statistical significance for rs743572 A > G (p=0.01, OR (Odds-Ratio) 0.30, 95%CI 0.12–0.79), rs6162 G >A (p=0.01, OR 3.33, 95% CI 1.27–8.72), rs6163 C > A (p=0.01, OR 3.33, 95% CI 1.27–8.72) and rs1004467 T > C (p=0.04, OR 2.43, 95%CI 1.03–5.73) in CYP17A1. There was no significant difference in SNPs of other genes between two groups. CONCLUSIONS Although larger validation study is needed, our study suggests that genetic polymorphisms in CYP17A1 are expected as good predictors for risk of progression in Japanese prostate cancer patients receiving androgen deprivation therapy. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e918 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Masashi Nakayama Osaka-city, Osaka, Japan More articles by this author Takeshi Yamada Suita, Osaka, Japan More articles by this author Tomohito Shimizu Suita, Osaka, Japan More articles by this author Shinpei Nonen Suita, Osaka, Japan More articles by this author Kensaku Nishimura Sakai, Osaka, Japan More articles by this author Kazuo Nishimura Osaka-city, Osaka, Japan More articles by this author Tsuneo Hara Ikeda, Osaka, Japan More articles by this author Go Tanigawa Osaka-city, Osaka, Japan More articles by this author Toshiaki Yoshioka Osaka-city, Osaka, Japan More articles by this author Koji Hatano Suita, Osaka, Japan More articles by this author Yasutomo Nakai Suita, Osaka, Japan More articles by this author Hitoshi Takayama Suita, Osaka, Japan More articles by this author Yasushi Fujio Suita, Osaka, Japan More articles by this author Junichi Azuma Suita, Osaka, Japan More articles by this author Akihiko Okuyama Osaka-city, Osaka, Japan More articles by this author Norio Nonomura Suita, Osaka, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...