Risk of Urinary Bladder Cancer Is Associated with 8q24 Variant rs9642880[T] in Multiple Racial/Ethnic Groups: Results from the Los Angeles-Shanghai Case-Control Study

Background: Multiple chromosome 8q24 genotypic variants are strongly implicated in several cancers. Recent genome-wide association studies of urinary bladder cancer report risk to be associated with the T allele of rs9642880 on 8q24 among individuals of European descent. Methods: We examined associations between bladder cancer risk and genotypes defined by rs9642880 and each of 8 additional 8q24 variants associated with risk of other cancers, in both high-risk non-Hispanic white and low-risk Chinese participants enrolled in a large population-based case-control study conducted in Los Angeles County and Shanghai. Results: We confirmed association of rs9642880 T with bladder cancer risk not only among non-Hispanic whites but also among Chinese participants [overall per-allele relative risk estimate 1.32 (95% CI, 1.16-1.50; P - 0.000024)]. Subgroup analyses suggested that effects of rs9642880 are largely confined to nonsmokers and former smokers, and may be particularly important in the etiology of noninvasive papillary tumors. There was little indication that 8q24 SNPs associated with other cancer types-rs7008482, rs7000448, rs6983561, rs6983267, rs13281615, rs13254738, or rs10090154-are associated with bladder cancer risk. Conclusions: Bladder cancer risk is associated specifically with variation in the discrete 8q24 region containing rs9642880. Factors other than rs9642880 genotypes seem to underlie differences in bladder cancer risk between non-Hispanic whites and Chinese. Impact: Characterization of functional consequences of genetic variation in the discrete region including rs9642880 is needed to understand biological basis of this bladder cancer-specific 8q24 association in these racial/ethnic groups characterized by both high and low risk of bladder cancer. Cancer Epidemiol Biomarkers Prev; 19(12); 3150-6. (C) 2010 AACR.