Association of CTLA-4 tagging polymorphisms and haplotypes with hepatocellular carcinoma risk A case-control study

Abstract

It has been proposed that cytotoxic T-lymphocyte antigen 4 (CTLA-4) may attenuate the T-cell activation threshold, thereby decreasing the antitumor response and conferring susceptibility to hepatocellular carcinoma (HCC). In the present study, we selected CTLA-4 tagging single nucleotide polymorphisms (SNPs) and explored the relationship between these polymorphisms and susceptibility to HCC. A hospital-based case-control study, comprising 584 cases with HCC and 923 controls, was performed in an eastern Chinese Han population. CTLA-4 SNPs were genotyped using a custom-by-design 48-Plex SNPscan Kit. We found that the CTLA-4 rs3087243 G>A polymorphism might be associated with increased risk of HCC (GA vs GG: adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.04-1.85; P=.028 and AA/GA vs GG: adjusted OR, 1.43; 95% CI, 1.08-1.89; P=.012). After using Bonferroni correction, this association remained (P=.012 for the AA/GA vs GG genetic model). In addition, the power value was 0.904 in the AA/GA versus GG genetic model. Haplotype analysis showed that CTLA4 Crs16840252Ars231775Ars3087243Trs733618, Crs16840252Grs231775Ars3087243Trs733618, and other haplotypes might increase the risk of HCC risk (P=.018, A polymorphism increases susceptibility to HCC in an eastern Chinese Han population. CTLA-4 haplotypes may influence the development of HCC. In the future, a population-based fine-mapping study with functional assessment should be performed to further determine these potential correlations. Abbreviations: CI = confidence interval, CTLA-4 = cytotoxic T-lymphocyte antigen 4, HBV = hepatitis B virus, HCC = hepatocellular carcinoma, HWE = Hardy-Weinberg equilibrium, IgSF = immunoglobulin superfamily, IL-2 = interleukin-2, OR = odds ratio, SNP = single nucleotide polymorphisms.