Investigation of Cytotoxic T-lymphocyte antigen 4 Polymorphisms in Gastric Cardia Adenocarcinoma

Abstract

To assess the potential effects of Cytotoxic T-lymphocyte antigen 4 (CTLA4) gene polymorphisms on susceptibility to gastric cardia adenocarcinoma (GCA), we genotyped four polymorphisms (rs733618 A>G, rs16840252 C>T, rs231775 G>A and rs3087243 G>A) in CTLA4 and calculated odds ratios (ORs) with the corresponding 95% confidence intervals (95% CIs) for the genotype and allele distributions between GCA cases and controls. The CTLA4 genotypes were determined by the polymerase chain reaction-ligase detection reaction (PCR-LDR) analysis in 330 GCA patients and 608 unrelated cancer-free controls. In this case-control study, there was no significant difference in the genotype and allele distributions of four CTLA4 polymorphisms between GCA patients and controls. However, haplotype association analysis indicated that compared with CTLA4 Grs733618Crs16840252Grs231775Crs3087243, CTLA4 Grs733618Crs16840252Ars231775Grs3087243 and Ars733618Crs16840252Grs231775Ars3087243 haplotypes conferred increased risks of GCA (OR = 6.46, 95% CI = 1.33-31.28; P = 0.012; both); however, CTLA4 Ars733618Crs16840252Ars231775Grs3087243 and Ars733618Trs16840252Grs231775Grs3087243 haplotypes conferred decreased risks of GCA (P = 0.001 and P = 0.011, respectively). These results highlight that the rare CTLA4 haplotypes may affect the development of GCA in the Chinese population.