title: Functional polymorphisms in cell death pathway genes FAS and FAS ligand and risk of prostate cancer in a Chinese population.
abstract: 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).
  
  
  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.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Shao
authors.forename: Qi
authors.initials: Q
authors.lastname: Ding
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Jialin
authors.initials: J
authors.lastname: Tang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.forename: Jiawei
authors.initials: J
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cao
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D053222:Fas Ligand Protein / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012306:Risk; D019014:fas Receptor / Q000235:genetics*
chemical_list: C491901:FAS protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor