| Background Hepatocellular carcinoma (HCC) is one of the most commonest malignancies in Guangxi, China. Aflatoxin B1 (AFB1) exposure which evokes DNA damage and gene mutation of the host cell is believed to be closely related to HCC in Guangxi.. Epidemiological evidences have shown that individuals have differently susceptible to AFB1 exposure, which may be correlated with the different DNA repair capacity of individuals.DNA damage induced by AFB1 can be repaired through nucleotide excision repair (NER) pathway that depends on DNA repair enzymes, such as Xeroderma Pigmentosum Group C (XPC). XPC participates in the initial recognition of DNA damage during the DNA nucleotide excision repair process The deficiency of this protein resulting from XPC codon 939 polymorphism (nucleotide change:A→C; amino acid change:Lys→Gln; RS#2228001) directly impacts the function of NER pathway. Recent molecular epidemiological studies have shown that XPC Lys939Gln polymorphism modifies the risk of skin and bladder cancers, however, its role in AFB1-related HCC is still unknown. Here we conducted a molecular epidemiological research to analyze the role of XPC Lys939Gln in the carcinogenesis of AFB1-related HCCMethods This study is a hospital-based case-control study. All subjects, including 98 HCC cases diagnosed through surgical pathology and 157 controls without any hepatic diseases evidence as well as the family history of tumors, are Guangxiese, from a high AFB1-exposure area. To control possible confounders, cases were frequently matched to controls based on age, gender, race, and Hepatitis viral B and C (HBV and HCV) infection. The levels of AFB1-DNA adducts of all subjects'peripheral blood white cells and XPC codon 939 genotypes were testified using competitive enzyme linked immunosorbent assay (Competitive-ELISA) and TaqMan-MGB-PCR method, respectively.Results We found HCC cases featured higher AFB1-DNA-adduct levels compared to controls (OR=2.45,95%CI=1.32-3.82). Chi-square test showed that the distribution of XPC codon 939 polymorphism was in accord with Hard-Weinberg Law. However, the frequent rate of Gln alleles at the codon 939 of XPC in the HCCs (39.3%) was higher than in the controls (30.9%), with increased near 0.5-time OR value (OR=1.45,95%CI=1.00-2.10) for Gln alleles and corresponding 0.7-time OR value for the genotypes containing Gln alleles. Intrestingly, female individuals having genotypes with Gln alleles, compared with those without risk genotypes (OR=1), would face significant higher risk of HCC (OR= 5.44,95%CI=1.38-21.50, P< 0.05). Additionally, the genotypes with codon 939 Gln of XPC interacted with AFB1-DNA-adduct levels in the carcinogenesis process of HCC (adjusted OR=3.70,95%CI= 1.63-8.41, P< 0.05), especially among female population (OR=12.60,95%CI =1.35-117.57, P< 0.05).Conclusions These results suggested that XPC Lys939Gln polymorphism might modify the risk of HCC and interact with AFB1 exposure in the carcinogenesis of HCC in Guangxi population, especially among female population. |
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