Association Between XPD Lys751Gln and Asp312Asn Polymorphisms and Hepatocellular Carcinoma Risk

Abstract

Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for DNA repair. Studies investigating the association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. The aim of this study was to quantitatively summarize the evidence for such an association.Eligible studies were identified by searching electronic databases including PubMed, Embase, Cochrane library, and CBM, Chinese Biomedical Literature Database, for the period up to October 2014. The association of XPD Lys751Gln and Asp312Asn polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).Finally, a total of 11 studies with 4322 cases and 4970 controls were included for XPD Lys751Gln polymorphism and 6 studies with 2223 cases and 2441 controls were available for XPD Asp312Asn polymorphism. With respect to XPD Lys751Gln polymorphism, statistically significant increased HCC risk was found when all studies were pooled into the meta-analysis (Gln/Gln vs Lys/Lys: OR = 1.363, 95% CI 1.065–1.744, P = 0.014; Lys/Gln vs Lys/Lys: OR = 1.205, 95% CI 1.099–1.321, P = 0.000; Gln/Gln+Lys/Gln vs Lys/Lys: OR = 1.300, 95% CI 1.141–1.480, P = 0.000). In subgroup analyses by ethnicity, source of control, Hardy–Weinberg equilibrium (HWE) in controls, hepatitis B virus (HBV) infection, and statistically significant increase of HCC risk was found in East Asians, population-based studies, studies consistent with HWE, and HBV-positive subjects, but not in mixed/other populations, hospital-based studies, studies deviating from HWE, and HBV-negative subjects. With respect to XPD Asp312Asn polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses.The results suggest that the XPD Lys751Gln polymorphism contributes to increased HCC susceptibility, especially in East Asian populations. Further, large and well-designed studies are required to validate this association.

Genetic Single Nucleotide Polymorphisms (GSNPs) in the DNA Repair Genes and Hepatocellular Carcinoma Related to Aflatoxin B1 among Guangxiese Population

“…This suggests that genetic susceptibility resulting from XPD GSNPs might have a potential efect on AFB1-related HCC risk among Guangxiese population. Meta-analysis further improved the above-mentioned hypothesis [56]. However, the studies from molecular epidemiological studies exhibit that another GSNP of XPD is not signiicantly correlate with the risk of HCC related to AFB1 [49,58].…”

“…To date, molecular epidemiological studies on two GSNPs in this gene, namely, rs369191500 polymorphism (codon 312, Asp to Asn) and rs13181 polymorphism (codon 751, Lys to Gln), have been conducted by diferent laboratories [54]. Genotype-phenotype analyses have shown that these two GSNPs are associated with low DNA repair ability, which might modify DNA-adduct levels, p53 gene mutation, and risk of cancer [55,56]. For genetic polymorphisms among Guangxiese population, a total of four epidemiological studies have been conducted via case-control design ( [58].…”

XPD Functions as a Tumor Suppressor and Dysregulates Autophagy in Cultured HepG2 Cells

“…XPD polymorphisms or changes in XPD expression have been associated with a wide array of malignancies [ 3 , 11 – 18 ]. With specific respect to HCC, recent studies have tied several unique XPD polymorphisms (e.g., Lys751Gln, Arg399Gln, and Asp312Asn) to increased HCC susceptibility [ 3 – 5 , 19 ].…”

Association between an insertion/deletion polymorphism in IL-1A gene and cancer risk: a meta-analysis

“… 1 Cancer is a multifactor disease resulting from the combined effect of genetic susceptibility and environmental factors. 2 – 4 The role of inflammation in carcinogenesis is a pivotal issue. Previous studies have demonstrated that inflammation-associated molecules are associated with a majority of cancer types, and these molecules are activated by various elements related to environment and lifestyle.…”