The association of six non-synonymous variants in three DNA repair genes with hepatocellular carcinoma risk: a meta-analysis.
Hepatocellular carcinoma is a complex polygenic disease. Despite the huge advances in genetic epidemiology, it still remains a challenge to unveil the genetic architecture of hepatocellular carcinoma. We, therefore, decided to meta-analytically assess the association of six non-synonymous coding variants from XRCC1, XRCC3 and XPD genes with hepatocellular carcinoma risk by pooling the results of 20 English articles. This meta-analysis was conducted according to the PRISMA statement, and data collection was independently completed in duplicate. In overall analyses, the minor alleles of four variants, Arg280His (odds ratio, 95% confidence interval, P: 1.37, 1.13-1.66, 0.001), Thr241Met (1.93, 1.17-3.20, 0.011), Asp312Asn (1.22, 1.08-1.38, 0.001) and Lys751Gln (1.42, 1.02-1.97, 0.038), were associated with the significant risk for hepatocellular carcinoma. There were low probabilities of publication bias for all variants. Subgroup analyses revealed significant association of XRCC1 gene Arg399Gln with hepatocellular carcinoma in Chinese especially from south China (odds ratio, 95% confidence interval, P: 1.57, 1.16-2.14, 0.004), in larger studies (1.48, 1.11-1.98, 0.007) and in studies with population-based controls (1.33, 1.06-1.68, 0.016). Taken together, our findings demonstrated that XPD gene Asp312Asn and XRCC1 gene Arg399Gln might be candidate susceptibility loci for hepatocellular carcinoma. Considering the ubiquity of genetic heterogeneity, further validation in a broad range of ethnic populations is warranted.
Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Yan-Hui
YH
Shi
Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
Bin
B
Wang
Intervention Therapy Department, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Bai-Ping
BP
Xu
Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Dan-Na
DN
Jiang
Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Dong-Mei
DM
Zhao
Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China.
Man-Ru
MR
Ji
Central Laboratory, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
Li
L
Zhou
Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China.
Xue
X
Li
Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China. changzhulu1998@163.com.
Chang-Zhu
CZ
Lu
D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
DNA repair gene; hepatocellular carcinoma; meta-analysis; non-synonymous variant; risk estimate