Sequence Variant on 3q28 and Urinary Bladder Cancer Risk: Findings from the Los Angeles-Shanghai Bladder Case-Control Study

摘要

Recently, the first genome wide association study of bladder cancer identified an association of genome-wide significance between SNP rs715021 and urinary bladder cancer risk among European individuals. This SNP is in a haplotype block in linkage disequilibrium with the TP63 gene. We investigated the role of this SNP among 1,042 cases and 1,123 controls among non-Latino whites in Los Angeles County, California, USA, and among Chinese in Shanghai, China. We confirmed an association between the A allele and bladder cancer risk (log-additive per A allele OR = 1.24; 95% CI = 1.02–1.52, p = 0.032) in Los Angeles County and a similar association in Shanghai (log-additive per A allele OR = 1.21; 95% CI = 0.98–1.49, p = 0.080). These estimates did not differ by study site, smoking status, or gender. However, the effects were greater in older individuals. Analysis within non-Latino whites for whom we had histological results, revealed that this association was restricted to low risk tumors (OR = 1.49, 95% CI = 1.17–1.92, p = 0.002) and absent among high-risk tumors (OR = 1.03, 95% CI = 0.80–1.33, p = 0.790; heterogeneity p = 0.019). A positive association (OR = 1.56; 95% CI = 0.93–2.62, p = 0.089) was only observed among high-risk tumors from individuals older than 56 years old (interaction p = 0.045). Our results suggest that a TP63 gene variant may increase susceptibility for the development of urinary bladder tumors with low risk of progression.