MP36-02 POLYMORPHISMS OF MEMBRANE TRANSPORTING GENE SLCO1B3 AND DETOXIFICATION ENZYME NAT2 ASSOCIATE WITH BLADDER CANCER SUSCEPTIBILITY IN SMOKERS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2015MP36-02 POLYMORPHISMS OF MEMBRANE TRANSPORTING GENE SLCO1B3 AND DETOXIFICATION ENZYME NAT2 ASSOCIATE WITH BLADDER CANCER SUSCEPTIBILITY IN SMOKERS Naohiro Fujimoto, Hoai Bui, Tatsuhiko Kubo, Hisato Inatomi, and Ryoichi Hamasuna Naohiro FujimotoNaohiro Fujimoto More articles by this author , Hoai BuiHoai Bui More articles by this author , Tatsuhiko KuboTatsuhiko Kubo More articles by this author , Hisato InatomiHisato Inatomi More articles by this author , and Ryoichi HamasunaRyoichi Hamasuna More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.730AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Varying combinations of genetic and environmental factors cause cancers including bladder cancer. Cigarette smoke contains lots of chemicals including over 60 well-established carcinogens and smoking is responsible for bladder cancer development. Cellular uptake and detoxification of carcinogens may play a role in cancer development. Organic anion-transporting polypeptides (OATPs) encoded by SLCOs mediate cellular uptake of a broad range of substrates including possible carcinogens. SLCOs are polymorphic, and single nucleotide polymorphisms (SNPs) of those genes alter transporting efficiency of substrates. We investigated the association between SNPs of SLCOs in combination with SNPs of NAT2 (detoxification enzyme) and bladder cancer risk in smokers in Japanese population. METHODS We analysed SNPs at rs2306283, rs4149117 and rs12422149 in SLCO1B1, SLCO1B3 and SLCO2B1, respectively, in 237 bladder cancer patients and 248 non-bladder cancer patients. Smoking status was grouped as smoker or never-smoker. SNPs were analyzed by DNA sequencing of peripheral blood cells. Combination effect of SLCO and NAT2 genotypes was also analyzed. NAT2 genotypes were divided into the rapid (wild type allele homo/heterozygotes: WT/WT, WT/M1-3) and the slow acetylator genotypes (two mutant alleles: M1-3/M1-3) RESULTS The number of smokers was 243 (143 in bladder cancer and 100 in non-bladder cancer patients).and bladder cancer was significantly frequent in smoker group (p<0,001). In non-smokers, polymorphisms of SLCOs were not associated with bladder cancer risk. In smokers, frequencies of SLCO1B3 G alleles and T alleles were 66.1% and 33.9% in bladder cancer patients, respectively, and 77.8% and 22.2% in non-bladder cancer patients, respectively. SLCO1B3 TT and TT/TG genotypes were at significantly higher risk of bladder cancer than GG genotype (TT vs GG: OR=4.75, p=0.011, TT/TG vs GG: OR=1.90, p=0.015). Genotypes of SLCO1B1 and SLCO2B1 were not associated with bladder cancer risk in smokers. In combination analyses of SLCO1B3 and NAT2 genotypes in smokers, the patients having SLCO1B3 TT/TG and NAT2 slow types were at significantly higher risk of bladder cancer than those with SLCO1B3 GG and NAT2 rapid genotypes (OR=3.95, p=0.014). CONCLUSIONS Our results, for the first time, demonstrated that genetic variants of SLCO1B3 rs4149117 were associated with bladder cancer risk and genetic variants of NAT2 further increased the risk. SLCO1B3 may be a potential biomarker for assessing the risk of bladder cancer development in smokers © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e428 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naohiro Fujimoto More articles by this author Hoai Bui More articles by this author Tatsuhiko Kubo More articles by this author Hisato Inatomi More articles by this author Ryoichi Hamasuna More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...