title: Functional polymorphisms in cell death pathway genes and risk of renal cell carcinoma.
abstract: The FAS/FAS ligand (FASL) system plays a key role in regulating apoptotic cell death, and corruption of this signaling pathway has been shown to participate in tumorigenesis. However, the effects of functional promoter polymorphisms of the CASP8, FAS, and FASL genes on risk of renal cell carcinoma (RCC) are unknown. In this study, we genotyped CASP8 -652 6N ins/del, FAS -1377 G > A, FAS -670 A > G, and FASL -844 C > T polymorphisms in a hospital-based case-control study of 353 patients diagnosed with RCC and 365 cancer-free controls in a Chinese population. Compared with CASP8 -652 ins/ins genotype, the del/del genotype had a significantly decreased RCC risk [adjusted odds ratio (OR) = 0.36, 95% confidence interval (CI) = 0.16-0.84]. For FAS -1377 G > A polymorphism, a significantly increased risk of RCC was found for AA (adjusted OR = 1.65, 95% CI = 1.03-2.64) and GA (adjusted OR = 1.41, 95% CI = 1.02-1.94) genotypes compared with GG genotype. When we combined these two polymorphisms together, we found that individuals carrying CASP8 -652 6N ins/del and FAS -1377 GG genotypes or CASP8 -652 6N del/del and FAS -1377 GG genotypes were associated with a statistically significantly decreased risk of RCC (adjusted OR = 0.46, 95% CI = 0.24-0.88 and OR = 0.12, 95% CI = 0.02-0.58, respectively) compared with individuals carrying CASP8 -652 6N ins/ins and FAS -1377 AA genotypes. These results suggest that the CASP8 -652 6N ins/del and FAS -1377 G > A polymorphisms are involved in the susceptibility to developing RCC in Chinese populations.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Fu
authors.initials: F
authors.lastname: Yan
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Ju
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Meng
authors.forename: Qi
authors.initials: Q
authors.lastname: Ding
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cao
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D005796:Genes; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D053222:Fas Ligand Protein; D053181:Caspase 8