title: Functional variants in cell death pathway genes and risk of pancreatic cancer.
abstract: OBJECTIVE
  Fas-Fas ligand (FasL)-mediated death pathway is important in the life and death of immune cells and, therefore, influences immune surveillance of carcinogenesis. This study examined the association between functional variants of Fas (-1377G-->A and -670A-->G), FasL (-844T-->C), and caspase-8 (CASP8) six-nucleotide deletion polymorphism (-652 6N ins-->del) and risk of pancreatic cancer.
  
  
  METHODS
  Genotypes were determined in 397 cases with pancreatic cancer and 907 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression, and all statistical tests were two sided.
  
  
  RESULTS
  We found a significant decrease in risk of pancreatic cancer associated with FasL and CASP8 but not Fas polymorphisms. Compared with noncarriers, the ORs of developing pancreatic cancer for FasL -844CT and TT carriers were 0.73 (95% CI, 0.57-0.94) and 0.35 (95% CI, 0.19-0.63), and for CASP8 -652 6N ins/del and del/del carriers were 0.65 (95% CI, 0.50-0.85) and 0.56 (95% CI, 0.33-0.98), respectively. Gene-gene interaction between the FasL and CASP8 variants further reduced the cancer risk in a multiplicative manner (OR for the presence of both FasL -844TT and CASP8 -652 6N del/del genotype, 0.10; 95% CI, 0.01-0.75). On the other hand, a multiplicative joint effect between the FasL -844CC or CASP8 -652 6N ins/ins genotype and smoking or diabetes mellitus in intensifying risk of pancreatic cancer was also evident.
  
  
  CONCLUSIONS
  These results suggest that genetic variations in the death pathway genes FasL and CASP8 are involved in susceptibility to developing pancreatic cancer.
authors.affiliation: Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
authors.forename: Junniao
authors.initials: J
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D003920:Diabetes Mellitus; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D019014:fas Receptor / Q000235:genetics
chemical_list: D053222:Fas Ligand Protein; D019014:fas Receptor; D053181:Caspase 8