Cumulative effect of genome-wide association study-identified genetic variants for bladder cancer

Recent genome-wide association studies have identified 14 genetic variants associated with bladder cancer in Caucasians. The effects of these risk variants and their cumulative effects in Asian populations are unknown. We genotyped these newly identified variants in a case-control study of 1,050 patients diagnosed with bladder cancer and 1,404 controls in the Chinese population. Odds rations (ORs) and 95% confidence intervals (CIs) were computed by logistic regression, and cumulative effect of risk alleles were evaluated. Overall, seven of the 14 variants were significantly associated with bladder cancer risk (p=9.763 x 10(-3) for rs9642880 at 8q24.21, p=3.004 x 10(-3) for rs2294008 at 8q24.3, p=0.012 for rs798766 at 4p16.3, p=0.034 for rs1495741 at 8p22, p=2.306 x 10(-4) for GSTM1, p=8.507 x 10(-8) for rs17674580 at 18q12.3, p=7.179 x 10(-4) for rs10936599 at 3q26.2) and the odds ratios (ORs) ranged from 1.13 to 1.65. Moreover, there were a significant increased risk for bladder cancer positively correlated numbers of risk alleles and smoking status (P-trend=7.060 x 10(-16)). However, no allelic interaction effects on bladder cancer risk were observed between cumulative effects of variants and clinical characteristics. These findings suggest that seven bladder cancer risk-associated variants (rs9642880, rs2294008, rs798766, rs1495741, GSTM1 null, rs17674580 and rs10936599) may be used, collectively, to effectively measure inherited risk for bladder cancer.