title: The functional cytotoxic T lymphocyte-associated Protein 4 49G-to-A genetic variant and risk of pancreatic cancer.
abstract: BACKGROUND
  Antitumor T lymphocytes play an essential part in immune surveillance of cancer cells. Cytotoxic T lymphocyte-associated Protein 4 (CTLA-4) is a negative regulator of T cell activation and proliferation and therefore influences immune surveillance of carcinogenesis of pancreas. Thus, this study examined the association between functional CTLA-4 49G-to-A (49G>A) single-nucleotide polymorphism and pancreatic cancer risk.
  
  
  METHODS
  Genotypes were determined in 368 patients with pancreatic cancer and 926 controls, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression.
  
  
  RESULTS
  A significant increased risk of pancreatic cancer was found to be associated with the CTLA-4 49G>A single-nucleotide polymorphism. Compared with noncarriers, the OR of developing pancreatic cancer for CTLA-4 49 GA or AA carriers was 1.75 (95% CI = 1.34-2.30, P = 4.83 × 10(-5) ) or 2.54 (95% CI = 1.67-3.87, P = 1.36 × 10(-5) ), respectively. In stratified analyses, the association was more pronounced in GA and AA carriers aged ≤60 years (OR = 3.10, 95% CI = 2.15-4.47, P(interaction) = .002), smokers with GA and AA genotypes (OR = 3.92, 95% CI = 2.39-6.43, P(interaction) = .037), and drinkers with GA and AA genotypes (OR = 4.55, 95% CI = 2.65-7.82, P(interaction) = .042), compared with GG carriers. Moreover, a supermultiplicative interaction between the CTLA-4 49AA genotype and smoking plus drinking was also evident in intensifying risk of pancreatic cancer (P(interaction) = 5.64 × 10(-12) ).
  
  
  CONCLUSIONS
  These results suggest that CTLA-4 49G>A polymorphism is involved in susceptibility to developing pancreatic cancer, alone and in a gene-environment interaction manner.
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. yangm@mail.buct.edu.cn
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Tang
authors.forename: Mo
authors.initials: M
authors.lastname: Zhou
authors.forename: Pengqun
authors.initials: P
authors.lastname: Kuang
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Yuan
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
mesh_terms: D000225:Adenine; D000367:Age Factors; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D048909:Diabetes Complications / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006147:Guanine; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
chemical_list: D060908:CTLA-4 Antigen; D006147:Guanine; D000225:Adenine