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XPD codon 312 and 751 polymorphisms, and AFB1 exposure, and hepatocellular carcinoma risk
BMC Cancer, 11/20/09

Long XD et al. – 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). 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. The findings of this study suggest that XPD Lys751Gln polymorphism is an important modulator of AFB1 related-HCC development.

Methods

Case-control study including 618 HCC cases and 712 controls to evaluate the associations between these 2 polymorphisms and HCC risk for Guangxi population by means of TaqMan-PCR and PCR-RFLP analysis

Results

Individuals featuring XPD genotypes with codon 751 Gln alleles (namely XPD-LG or XPD-GG) related to elevated risk of HCC compared to those with homozygote of XPD codon 751 Lys alleles [namely XPD-LL, adjusted odds ratios (ORs) 1.75 and 2.47; 95% confidence interval (CIs) were 1.30 - 2.37 and 1.62 - 3.76, respectively]
Gender-specific role evident that showed higher risk for women (adjusted OR was 8.58 for XPD-GG) than for men (adjusted OR = 2.90 for XPD-GG)
Interactive effects of polymorphism and AFB1-exposure information showed codon 751 Gln alleles increase risk of HCC for individuals facing longer exposure years (Pinteraction = 0.011, OR = 0.85)
Long-exposure-years (> 48 years) individuals who carried XDP-GG had adjusted OR of 470.25, whereas long-exposure-years people with XDP-LL were lower risk (adjusted OR = 149.12)
Did not find XPD codon 312 polymorphism significantly associated with HCC risk