Genetic variations and haplotypes in TIM-3 gene and the risk of gastric cancer.

ABSTRACT

PURPOSE: T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) could weaken the Th1-mediated anti-tumor responses and accelerate the tumor cell proliferation by inhabiting the production of IL-2 or IFN-γ. This study was to assess the association between TIM-3 genetic variations and the development of gastric cancer. PATIENTS AND METHODS: Five polymorphisms located in the promoter or encoding region of TIM-3 gene were genotyped in 212 gastric cancer patients and 252 controls who matched with the patients on the frequency of age, gender, smoking, and drinking. Logistic regression was used to determine whether the inherited variations within TIM-3 gene were associated with gastric cancer risk. Linkage disequilibrium and Haplotype analyses were performed by using SHEsis program. RESULTS: By the individual genotype analysis, three polymorphisms (-574G/T, -882C/T, and -1516G/T) within TIM-3 gene were significantly associated with gastric cancer in the study population [ORs (95% CIs) 2.74 (1.21-6.20), 3.19 (1.29-7.91), and 2.03 (1.15-3.59); respectively]. Among the gastric cancer patients, the relationship between the -1516 polymorphic genotype and the distant metastasis of tumor was found (OR = 2.21, 95% CI = 1.05-4.63). Under the analysis of haplotypes, an even stronger association with haplotype TTGCT was observed in gastric cancer risk (OR = 5.57, 95% CI 1.04-29.80, P = 0.024). CONCLUSION: These results indicated that the three genetic variations within the TIM-3 gene promoter may be associated with the increased susceptibility to gastric cancer, especially among the haplotypes with the risk.