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The functional cytotoxic T lymphocyte–associated Protein 4 49G‐to‐A genetic variant and risk of pancreatic cancer
Author(s) -
Yang Ming,
Sun Tong,
Zhou Yifeng,
Wang Li,
Liu Li,
Zhang Xiaojiao,
Tang Xiaohu,
Zhou Mo,
Kuang Pengqun,
Tan Wen,
Li Hui,
Yuan Qipeng,
Yu Dianke
Publication year - 2012
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.27455
Subject(s) - pancreatic cancer , odds ratio , medicine , genotype , cytotoxic t cell , pancreas , confidence interval , cancer , immune system , gastroenterology , logistic regression , immunology , oncology , endocrinology , biology , genetics , gene , in vitro
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. Cancer 2012. © 2012 American Cancer Society.