Functional polymorphisms in cell death pathway genes FAS and FAS ligand and risk of prostate cancer in a Chinese population.

Background: Apoptosis is the physiological mechanism of programmed cell death and abnormal regulation of this pathway can lead to carcinogenesis. We hypothesized that the FAS -1377G>A, -670A>G, and FASL -844T>C polymorphisms are associated with risk of prostate cancer (PCa).
Materials and Methods: We genotyped polymorphisms in a hospital-based case-control study of 602 patients diagnosed with PCa and 703 cancer-free controls in a Chinese population using polymerase chain reaction-restriction fragment length polymorphism method.
Results: We found a significantly decreased risk associated with FAS -1377GA [adjusted odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.56-0.90] genotype compared with the -1377GG genotype and decreased risk associated with FAS -670AG and -670GG genotypes (OR 0.75, 95% CI: 0.59-0.95; OR 0.70, 95% CI: 0.50-0.96) compared with the -670AA genotype. Consistently, we found that individuals carrying haplotype genotype with 0 or 1 risk allele (-1377G and -670A) had a lower risk of PCa than those with two risk alleles (OR 0.48, 95% CI: 0.28-0.80; OR 0.60, 95% CI: 0.41-0.87; OR 0.82, 95% CI: 0.69-0.97 for the AA, GG, and AG haplotype, respectively). In addition, when we evaluated these two FAS polymorphisms together, we found that the combined genotype with 4 risk alleles was associated with a significantly increased risk of PCa compared with those with 0-3 variants (OR 1.51, 95% CI: 1.19-1.91), and this increased risk was more pronounced among subgroups of Gleason score <7 and >7, and PSA > 20 ng/ml (OR 1.49, 95% CI: 1.08-2.04; OR 1.72, 95% CI: 1.25-2.44; OR 1.61, 95% CI: 1.23-2.13, respectively).
Conclusions: These results suggested that the FAS polymorphisms may contribute to PCa risk in a Chinese population.
(Copyright © 2011 Wiley-Liss, Inc.)