The functional cytotoxic T lymphocyte-associated Protein 4 49G-to-A genetic variant and risk of pancreatic cancer.

Journal: Cancer
Published:
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
Ming Yang, Tong Sun, Yifeng Zhou, Li Wang, Li Liu, Xiaojiao Zhang, Xiaohu Tang, Mo Zhou, Pengqun Kuang, Wen Tan, Hui Li, Qipeng Yuan, Dianke Yu
Relevant Conditions

Pancreatic Cancer