Correlation of CTLA-4 polymorphism and the risk of gastric cancer in a Chinese Bai population.

Abstract

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is involved in the regulation of immune responses mediated by T cells. This study aimed to explore the correlation between CTLA-4 gene polymorphisms and the risk of gastric cancer (GC) in the Bai minority population of southwestern China. A total of 422 GC patients and 397 healthy controls (HC) were included in this case-control study. Four single nucleotide polymorphism sites of CTLA-4 gene (rs231775, rs733618, rs16840252 and rs3087243) were selected and analysed. The results showed a significant difference in the rs733618 loci between GC and HC groups. The frequency of the rs733618 polymorphism 'TC' genotype was significantly lower in GC group compared to the HC group [odds ratio (OR), 95% confidence interval (CI): .47 (.35-.63), p<.001]. GC cases with dominant genetic model 'TC+CC' had a 47% reduced risk of GC [OR, 95%CI: .53 (.40-.71), p<.001]. Subgroup analyses revealed that the rs733618 'TC+CC' genotype was associated with a lower risk of GC in male patients [OR, 95%CI: .42 (.31-.58), p<.001], those aged ≤60 years old [OR, 95%CI: .27 (.18-.42), p<.001], non-drinkers [OR, 95%CI: .21 (.13-.33), p<.001], non-smokers [OR, 95%CI: .38 (.25-.57), p<.001] and individuals without Helicobacter pylori infection [OR, 95%CI: .16 (.10-.26), p<.001]. Further multivariated analyses indicated that individuals with the 'TC+CC' rs733618 genotype who were aged ≤60 years old [OR, 95%CI: .42 (.29-.83), p=.032] and had no H. pylori infection [OR, 95%CI: .35 (.28-.76), p=.018] were found to have a protective effect against GC. Additionally, soluble CTLA-4 were significantly lower in GC patients with 'TC' and 'TC+CC' genotypes (all p<.05). Our findings suggest that the rs733618 polymorphism of CTLA-4 gene may play a critical role in the prevention of GC.