Association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma risk: a systematic review and meta-analysis

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.

FIGURE 1

Forest plots of XPD Lys751Gln polymorphism and HCC risk in subgroup analysis by ethnicity using a random-effects model (dominant model Gln/Gln+Lys/Gln vs Lys/Lys). Gln = glutamine, HCC = hepatocellular carcinoma, Lys = lysine, OR = odds ratio, XPD = xeroderma pigmentosum group D.

FIGURE 2

Forest plots of XPD Asp312Asn polymorphism and HCC risk in subgroup analysis by source of controls using a random-effects model (recessive model Asn/Asn vs Asp/Asn+Asp/Asp). Asn = asparagine amino acid, Asp = aspartic acid, HB = hospital-based studies, HCC = hepatocellular carcinoma, OR = odds ratio, PB = population-based studies, XPD = xeroderma pigmentosum group D.

FIGURE 3

Galbraith plots of XPD Lys751Gln polymorphism and HCC risk (dominant model Gln/Gln+Lys/Gln vs Lys/Lys). The study by Jiang et al was spotted as the outlier. Gln = glutamine, HCC = hepatocellular carcinoma, Lys = lysine, XPD = xeroderma pigmentosum group D.

FIGURE 4

Galbraith plots of XPD Asp312Asn polymorphism and HCC risk (recessive model Asn/Asn vs Asp/Asn+Asp/Asp). The study by Zeng et al was spotted as the outlier. Asn = asparagine amino acid, Asp = aspartic acid, HCC = hepatocellular carcinoma, XPD = xeroderma pigmentosum group D.

FIGURE 5

Funnel plot analysis to detect the publication bias. Each point represents a single study for the indicated association. (A) Funnel plot for XPD Lys751Gln polymorphism in overall analysis (dominant model Gln/Gln+Lys/Gln vs Lys/Lys: P = 0.543). (B) Funnel plot for XPD Asp312Asn polymorphism in overall analysis (recessive model Asn/Asn vs Asp/Asn+Asp/Asp: P = 0.977). Asn = asparagine amino acid, Asp = aspartic acid, Gln = glutamine, Lys = lysine, XPD = xeroderma pigmentosum group D.