MP70-09 IDENTIFICATION OF NINE NEW SUSCEPTIBILITY LOCI FOR PROSTATE CANCER IN THE JAPANESE POPULATION

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology III1 Apr 2018MP70-09 IDENTIFICATION OF NINE NEW SUSCEPTIBILITY LOCI FOR PROSTATE CANCER IN THE JAPANESE POPULATION Ryo Takata, Shusuke Akamatsu, Hidewaki Nakagawa, Naoki Terada, Yoichiro Kato, Mitsugu Kanehira, Jun Sugimura, So Omori, Takaya Abe, Johji Inazawa, Osamu Ogawa, and Wataru Obara Ryo TakataRyo Takata More articles by this author , Shusuke AkamatsuShusuke Akamatsu More articles by this author , Hidewaki NakagawaHidewaki Nakagawa More articles by this author , Naoki TeradaNaoki Terada More articles by this author , Yoichiro KatoYoichiro Kato More articles by this author , Mitsugu KanehiraMitsugu Kanehira More articles by this author , Jun SugimuraJun Sugimura More articles by this author , So OmoriSo Omori More articles by this author , Takaya AbeTakaya Abe More articles by this author , Johji InazawaJohji Inazawa More articles by this author , Osamu OgawaOsamu Ogawa More articles by this author , and Wataru ObaraWataru Obara More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2253AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PC) is one of the most common malignancies in males throughout the world. Although the mechanisms by which prostate cancer develops and progresses are not clear, there is considerable evidence that genetic factors are important in its etiology. Recent genome-wide association studies (GWAS) have identified common variants at multiple loci that have moderate effects on PC risk. However, GWAS for prostate cancer have been undertaken exclusively among European populations. Further GWAS of Asian and other ethnic populations are required to identify additional susceptibility loci for PC and to enhance the understanding of the complex genetic effect on prostate carcinogenesis. To identify genetic factors that confer risk of PC in the Japanese population, we carried out extensive GWAS using Japanese case and controls. METHODS We carried out a genome-wide association study of 511,810 SNPs using 5,088 Japanese men with PC and 10,682 healthy control subjects. We obtained 7,521,072 SNPs information by imputation using 1000 Genomes Project data. In addition, we conducted replication study in an independent set of 4,818 Japanese PC patients and 73,261 control subjects. RESULTS From the 108 associated SNPs reported in previous GWAS, we confirmed the association of 49 SNPs at P < 0.05 in the Japanese population. The remaining 59 SNPs showed no association (P > 0.05). Therefore, it became evident that the SNPs associated with PC pathogenesis greatly varies depending on race. In addition, we performed replication study for 101 SNPs which indicated P < 1.0 x 10-5 in the GWAS. As a result, we identified nine new loci for PC susceptibility at 1p36, 8q24, 10q22, 12p13, 12q21, 15q22, 20p13 and 22q13 (P = 3.34 x 10-8 - 5.28 x 10-20). Moreover, the polymorphisms of SNP and the expression of the surrounding gene showed a significant correlation with QTL analysis in the 2 associated SNPs. CONCLUSIONS This study had an advantage of eliminating of affect for genetic heterogeneity, since we conducted GWAS using genetically quite a homogeneous population of Japanese. These findings advance our understanding of the genetic basis of prostate carcinogenesis and highlight the genetic heterogeneity of PC susceptibility among different ethnic populations. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e937 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Ryo Takata More articles by this author Shusuke Akamatsu More articles by this author Hidewaki Nakagawa More articles by this author Naoki Terada More articles by this author Yoichiro Kato More articles by this author Mitsugu Kanehira More articles by this author Jun Sugimura More articles by this author So Omori More articles by this author Takaya Abe More articles by this author Johji Inazawa More articles by this author Osamu Ogawa More articles by this author Wataru Obara More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...