Polymorphisms of UGT1A7 and XRCC1 are associated with an increased risk of hepatocellular carcinoma in Northeast China

Abstract

Objective: Hepatocellular carcinoma (HCC) is a complex disease which associates with both environmental and genetic factors. The purpose of this study was to investigate whether the genetic polymorphisms of UDPglucuronosyltransferase(UGT1A7), an important phase II biotransformation enzyme, and X-ray repair crosscomplementing group 1(XRCC1), a pivotal DNA-repair gene, were related to the risk of HCC in Northeast China.Methods: One hundred and thirty six HCC patients and one hundred and thirty six frequency-matched controls were included in this hospital-based case-control study. Genotypes of UGT1A7 and XRCC1 were determined using allele-specific polymerase chain reaction (AS-PCR) and PCR-restriction fragment length polymorphism (RFLP), and for which the odds ratio (OR) with 95% confidence interval (95% CI) were calculated.Results: The proportion of UGT1A7 low enzymatic allele ( * 2 or * 3) was higher in HCC patients than those in controls. The UGT1A7 * 1/ * 2 and * 3/ * 3 genotypes were associated with higher HCC risk (OR=2.09, 95%CI: 1.10-3.97; OR=5.67, 95%CI: 1.76-18.30, respectively). The XRCC1 codon 399 Arg/Gln genotype could also elevate HCC risk (OR=2.16, 95% CI 1.29-3.61). In addition to polymorphisms of UGT1A7 and XRCC1, multivariate logistic regression analysis demonstrated that other significant independent factors associated with HCC were HBV infection (OR=68.07, HCV infection (OR=30.97,) and family history of HCC (OR=10.62, 95%CI: 2.22-50.77).Conclusion: The study shows that the polymorphisms of UGT1A7 and XRCC1 are associated with HCC risk. Determination of the polymorphisms of UGT1A7 and XRCC1 may provide an important clue to preventive measure against HCC.

Host genetic factors associated with hepatocellular carcinoma in patients with hepatitis C virus infection: A systematic review

“…UDP glucuronosyltransferase 1 family, polypeptide A7, is encoded by the UGT1A7 gene. Five of the six studies which focused on UGT1A7 used HCC as an outcome, and all but one of these found a significant association. A total of 1450 patients made up these studies, and they used a variety of control groups including HCV‐infected patients and three studies using healthy controls.…”

The XRCC1 Arg399Gln Genetic Polymorphism Contributes to Hepatocellular Carcinoma Susceptibility: An Updated Meta-analysis

“…A flow diagram summarizing the process of study selection was illustrated in Figure 1. As summarized in Table 1, the final data pooling consisted of 15 eligible publications (Long et al, 2005;Kirk et al, 2005;Chen et al, 2005;Long et al, 2006;Borentain et al, 2007;Ren et al, 2008;Jia et al, 2010;Zeng et al, 2010;Pan et al, 2011;Tang et al, 2011;Li et al, 2012;Mohana Devi et al, 2013;Gulnaz et al, 2013) (eleven in English (Long et al, 2005;Kirk et al, 2005;Chen et al, 2005;Long et al, 2006;Borentain et al, 2007;Jia et al, 2010;Pan et al, 2011;Li et al, 2012;Mohana Devi et al, 2013;Gulnaz et al, 2013) and four (Ren et al, 2008;Zeng et al, 2010;Tang et al, 2011) in Chinese) with a mount of 2719 HCC cases and 3837 controls.…”

Associations between three XRCC1 polymorphisms and hepatocellular carcinoma risk: A meta-analysis of case-control studies

“…Su et al [ 10 ] suggested that the Arg194Trp and Arg280His polymorphisms are not related to susceptibility to HCC but that the Arg399Gln polymorphism is a susceptibility factor for HCC, with Gln/Gln as a risk factor, consistent with the results of this study. Jia et al [ 35 ] found that the XRCC1 399 Arg/Gln genotype conferred increased HCC risk. Han et al [ 16 ] found that the median survival rate of individuals carrying the XRCC1 Gln/Gln genotype was significantly lower than that of individuals carrying the XRCC1 Arg/Arg genotype.…”