A functional insertion/deletion polymorphism in the proximal promoter of CD3G is associated with susceptibility for hepatocellular carcinoma in Chinese population

Abstract

Hepatocellular carcinoma (HCC) represents the most common primary malignancy of the liver with a worldwide increasing incidence. Although the risk factors for HCC are well characterized, the molecular mechanisms responsible for malignant transformation of hepatocytes are not well understood. In this study, a case-control study including 291 HCC patients and 294 healthy controls was conducted to investigate the association between HCC susceptibility and with a 4-bp insertion/deletion polymorphism (rs66465034) in the proximal promoter of CD3G. Logistic regression analysis showed that the heterozygote and the homozygote 4-bp ins/ins confer a significantly increased risk of HCC after controlling for other covariates (adjusted odds ratio [OR]=1.51, 95% confidence interval [C.I.] 1.01-2.27, p=0.040; OR=1.71, 95% C.I. 1.07-2.89, p=0.025, respectively). Carriage of the 4-bp insertion allele was associated with a greatly increased risk of developing the disease (OR=1.30, 95% C.I. 1.02-1.64, p=0.027). Moreover, hepatitis B virus (HBV) stratification analysis showed that the differences between cases and controls were more obvious in HBV-positive than in the HBV-negative population, suggesting a possible role of this polymorphism in the immune regulation during HBV infection. Further, luciferase-based transient transfection assays revealed that rs66465034 can affect promoter activity of CD3G, indicating its possible functional significance. Our data suggested that common genetic polymorphisms in CD3G may influence HCC risk in Chinese population. Considering the relative small sample size, replication in other populations with larger sample size and further functional analysis are required for fully understanding the roles of CD3G polymorphisms in predisposition for HCC.

FIG. 1.

Polyacrylamide gel electrophoresis analysis of 4-bp insertion/deletion CD3G polymorphism. The deletion allele corresponds to the 132-bp fragment, and the insertion allele corresponds to the 136-bp fragment. Lanes 1, 2: homozygous (deletion/deletion); lanes 3, 5–7, 10, 11: heterozygous (insertion/deletion); lanes 8, 9: homozygous (insertion/insertion); lane 4, negative control.

FIG. 2.

Luciferase expression of two constructs in HepG2 and sk-Hep-1 cells co-transfected with pRL-TK to standardize transfection efficiency. *p<0.01 compared with deletion construct.