Abstract

Hepatocellular carcinoma (HCC) is a serious public health issue, the incidence of which is considered to be closely related to tobacco smoking, alcohol consumption, hepatitis B virus (HBV) infection and family history. The DNA repair system is an important protective mechanism against the development of malignant cells induced by internal and external environmental factors. The aim of this study was to investigate the association of polymorphisms of XRCC1-194, XRCC1-280 and XPD-312 DNA repair genes and the risk of development of HCC in Han Chinese patients. A case-control design was used including 252 HCC inpatients and 250 healthy controls recruited and matched by age, gender, tobacco smoking, alcohol consumption, HBV infection and family history. XPD Asp312Asn, XRCC1 Arg194Trp and XRCC1 Arg280His genes were examined using a sequencing assay method. Distributions of the genotype frequency and odds ratio (OR) between the two groups were analyzed. The results demonstrated that there was no significant difference in the frequencies of XPD Asp312Asn, XRCC1 Arg194Trp and XRCC1 Arg280His in the HCC cases and the control group. In the stratified analysis of different allele genotypes, the frequency of the XRCC1-194 site genotype was not significantly different between the case and control group. The presence of the XRCC1 280His genotype was associated with a significantly increased risk of HCC under conditions of HBV infection and family history [OR (95% CI): 1.68 (1.08-2.60), 4.20 (1.34-13.20), respectively]. Similarly, the XPD 312Asn significantly increased the risk of HCC under conditions of alcohol consumption, tobacco smoking, HBV infection and family history [OR (95% CI): 1.67 (1.10-2.60), 1.87 (1.18-2.96), 1.96 (1.24-3.10), 3.40 (1.32-8.76), respectively]. In conclusion, tobacco smoking and alcohol consumption are high risk factors of HCC for the XPD 312Asn genotype; HBV infection and family history increase the risk of HCC for the genotypes XRCC1 280His and XPD 312Asn.

Highlights

  • Hepatocellular carcinoma (HCC) is a common type of malignant tumor with a mortality rate of 20/100,000

  • There was no difference between the two groups in terms of age, gender, tobacco smoking, alcohol consumption, family history and hepatitis B virus (HBV) infection status (Table I)

  • Defective or lowered repair capacity of DNA caused by the polymorphisms of DNA repair genes increases the risk of mutations and carcinogenesis [8]

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Summary

Introduction

Hepatocellular carcinoma (HCC) is a common type of malignant tumor with a mortality rate of 20/100,000. It is often aggressive with rapid development, which seriously threatens life and health. It has been found that human gene polymorphisms may be associated with genetic susceptibility for cancer. The interaction of environmental factors and genetic polymorphisms may play a crucial role in tumor development. Epidemiological studies suggest that chronic hepatitis B virus (HBV) infection, aflatoxin B1 (AFBl) intake in food, and longterm excessive alcohol consumption are major environmental risk factors for HCC. The relationship between genetic polymorphisms and susceptibility to HCC, and the relationship between HCC and the interaction of environmental factors and genetic polymorphisms are still poorly understood [1]

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