rs710521

A three-stage fine mapping study of the 3q28 bladder cancer susceptibility locus identified rs35592567 in the 3'-UTR of TP63 as a functional causal variant. The T allele was significantly associated with decreased bladder cancer risk (OR=0.82, 95% CI=0.75-0.90, P=9.797×10⁻⁶). Functional studies showed the variant affects miR-140-5p binding, regulating TP63 post-transcriptional levels and affecting bladder cancer cell proliferation, migration, and invasion.

This case-control study of 231 bladder urothelial carcinoma (UC) patients and 261 benign controls found that rs9642880[T] and rs798766[T] variants increase bladder-UC risk (OR=1.72, p=0.028 and OR=1.84, p=0.01 respectively), but unlike upper tract UC, these variants are not associated with disease aggressiveness (grade or stage). The findings highlight distinct genetic differences between bladder-UC and upper urinary tract urothelial carcinoma.

A case-control study of 1,425 bladder cancer cases and 1,740 controls confirmed that rs710521[A] on chromosome 3q28 near TP63 is significantly associated with increased urinary bladder cancer risk (OR = 1.21 in unadjusted analysis, P = 0.011; OR = 1.23 in multivariate analysis adjusted for age, gender, smoking, and ethnicity, P = 0.010). Meta-analysis of 5,695 cases and 40,187 controls yielded a highly significant association (OR = 1.18, P < 0.0001), though the effect size is modest. No interaction was found with smoking or occupational exposure to bladder carcinogens.