Abstract
BackgroundGenetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of hepatocellular carcinoma (HCC) related to the exposure of aflatoxin B1 (AFB1). In this study, we have focused on the polymorphisms of xeroderma pigmentosum complementation group D (XPD) codon 312 and 751 (namely Asp312Asn and Lys751Gln), involved in nucleotide excision repair.MethodsWe conducted a case-control study including 618 HCC cases and 712 controls to evaluate the associations between these two polymorphisms and HCC risk for Guangxi population by means of TaqMan-PCR and PCR-RFLP analysis.ResultsWe found that individuals featuring the XPD genotypes with codon 751 Gln alleles (namely XPD-LG or XPD-GG) were related to an elevated risk of HCC compared to those with the homozygote of XPD codon 751 Lys alleles [namely XPD-LL, adjusted odds ratios (ORs) were 1.75 and 2.47; 95% confidence interval (CIs) were 1.30-2.37 and 1.62-3.76, respectively]. A gender-specific role was evident that showed an higher risk for women (adjusted OR was 8.58 for XPD-GG) than for men (adjusted OR = 2.90 for XPD-GG). Interestingly, the interactive effects of this polymorphism and AFB1-exposure information showed the codon 751 Gln alleles increase the risk of HCC for individuals facing longer exposure years (Pinteraction = 0.011, OR = 0.85). For example, long-exposure-years (> 48 years) individuals who carried XDP-GG had an adjusted OR of 470.25, whereas long-exposure-years people with XDP-LL were at lower risk (adjusted OR = 149.12). However, we did not find that XPD codon 312 polymorphism was significantly associated with HCC risk.ConclusionThese findings suggest that XPD Lys751Gln polymorphism is an important modulator of AFB1 related-HCC development in Guangxi population.
Highlights
Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of hepatocellular carcinoma (HCC) related to the exposure of aflatoxin B1 (AFB1)
We have previously reported a relationship between HCC risk and allelic variations in the X-ray repair cross-complementing group 1 (XRCC1) and XRCC3 genes which are involved in base excision repair (BER) and strand break repair pathway [6,7]
Demographic and etiologic characteristics for subjects There were no significant differences for sex, age, ethnicity, hepatitis B surface antigen (HBsAg) and anti-hepatic C virus (HCV) status (P > 0.05; Table 1), which suggested HCC patients' data are comparable with controls'
Summary
Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of hepatocellular carcinoma (HCC) related to the exposure of aflatoxin B1 (AFB1). We have focused on the polymorphisms of xeroderma pigmentosum complementation group D (XPD) codon 312 and 751 (namely Asp312Asn and Lys751Gln), involved in nucleotide excision repair. We have previously reported a relationship between HCC risk and allelic variations in the X-ray repair cross-complementing group 1 (XRCC1) and XRCC3 genes which are involved in BER and strand break repair pathway [6,7]. We focused on the xeroderma pigmentosum complementation group D (XPD) gene, which is one of the seven genetic complementation groups encoding for proteins involved in the NER pathway [5,8,9]. We conducted a hospital-based case-control study to examine whether these two polymorphisms modify the risk of HCC among Guangxi population from an AFB1 exposure area
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