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FAS and FASLG together initiate apoptosis, which prevents tumor development. FAS and FASLG polymorphisms in the promoter regions can alter the transcriptional activities and thus alter risk of cancer. We hypothesized that the FAS −1377G>A, −670A>G, and FASLG −844T>C polymorphisms are associated with risk of bladder cancer.In a hospital-based case–control study of 216 case patients with newly diagnosed bladder transitional cell carcinoma and 252 cancer-free controls frequency-matched by age and sex, we genotyped polymorphisms using PCR–restriction fragment length polymorphism.We found a statistically significantly increased risk of bladder cancer associated with the FASLG −844CC genotype [adjusted OR=1.51; 95% CI 1.03–2.23] compared with −844 (CT+TT). Consistently, the FAS haplotype genotypes with 2–4 variant (risk) alleles (−1377A and −670A) were associated with an increased risk of bladder cancer compared to 0–1 variants (OR=2.14; 95% CI 1.10–4.16). Furthermore, when we evaluated these three polymorphisms together, we found that the combined genotypes with 4–6 variant (risk) alleles (−1377A, −670A, and −844C) were associated with an increased risk of bladder cancer (OR=1.58; 95% CI 1.07–2.34) compared to 1–3 variants, and this increased risk was more pronounced among subgroups of aged >50 years (OR=1.70; 95% CI 1.11–2.61) and smokers (OR=1.88; 95% CI 1.06–3.32).FAS and FASLG polymorphisms appear to jointly contribute to risk of bladder cancer in this southern Chinese population. Larger studies are needed to verify these findings.