Association of genetic polymorphisms in STAT1 gene with increased risk of hepatocellular carcinoma

Objective: Although signal transducer and activator of transcription 1 (STAT1), a transcription factor, plays a critical role in carcinogenesis and has been implicated as a tumor suppressor, few studies have investigated the associations between polymorphisms of this gene and the risk of cancer development. The aim of this study was to examine whether STAT1 gene polymorphisms are associated with the risk of hepatocellular carcinoma (HCC). Methods: Ten single nucleotide polymorphisms in the STAT1 gene were genotyped by TaqMan assays in 469 HCC cases and 558 age-, sex- and HBsAg-matched controls in a Chinese population. Results: Minor allele homozygous genotypes at rs867637 (9,046 bp 3′ of STP A>G), rs3771300 (IVS24-153T>G), and rs2280235 (IVS20-103G>A), compared with their homozygote genotypes of common alleles, were associated with 1.6- (95% CI 1.1-2.3), 1.6- (95% CI 1.1-2.4), and 1.4-fold (95% CI 0.95-1.9) increased risk of HCC, respectively. The GGA haplotype, comprised of risk alleles at rs867637, rs3771300 and rs2280235, conferred a 1.2-fold (95% CI 1.0-1.5) increased risk of HCC, as compared to the most common haplotype of ATG. Diplotype GGA/GGA conferred a 1.6-fold (95% CI 1.0-2.5) increased risk of HCC compared with diplotype ATG/ATG. Conclusion: Our results demonstrate for the first time that polymorphisms in the STAT1 gene are associated with HCC susceptibility.