The effect of XPD/ERCC2 polymorphisms on gastric cancer risk among different ethnicities: a systematic review and meta-analysis

PLoS One. 2012;7(9):e43431. doi: 10.1371/journal.pone.0043431. Epub 2012 Sep 13.

Abstract

Background: Potential xeroderma pigmentosum group D (XPD), also called excision repair cross-complimentary group two (ERCC2), Lys751Gln and Asp312Asn polymorphisms have been implicated in gastric cancer risk among different ethnicities.

Methods: We aimed to explore the effect of XPD Lys751Gln and Asp312Asn polymorphisms on the susceptibility to gastric cancer among different ethnicities through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. 13 studies were ultimately eligible for the meta-analysis of Lys751Gln polymorphism and 9 studies for the meta-analysis of Asp312Asn polymorphism. We adopted the most probably appropriate genetic model (recessive model) for both Lys751Gln and Asp312Asn polymorphisms. Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication biases were estimated.

Results: Statistically significant findings were apparently noted in Asians but not in Caucasians for both XPD Lys751Gln and XPD Asp312Asn polymorphisms. A statistically significant finding could be seen in noncardia-type gastric cancer for XPD Lys751Gln polymorphism. A statistically significant finding could also be seen in high quality subgroup, small-and-moderate sample size subgroup, articles published after 2007, or PCR-RFLP genotyping subgroup for XPD Asp312Asn polymorphism.

Conclusions: Our meta-analysis indicates that XPD Gln751Gln (CC) genotype and Asn312Asn (AA) genotype may seem to be more susceptible to gastric cancer in Asian populations but not in Caucasian populations, suggesting that the two genotypes may be important biomarkers of gastric cancer susceptibility for Asian populations, the assumption that needs to be further confirmed in well-designed studies among different ethnicities. Gln751Gln (CC) genotype may also be associated with noncardia-type gastric cancer risk, which should also be confirmed among different ethnicities in the future.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Asian People / genetics
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Publication Bias
  • Stomach Neoplasms / ethnology*
  • Stomach Neoplasms / genetics*
  • White People / genetics
  • Xeroderma Pigmentosum Group D Protein / genetics*

Substances

  • Xeroderma Pigmentosum Group D Protein

Grants and funding

This work has been supported by The National Natural Science Foundation of China (grants 30830038, 30970842, and 81071180); “973” Project (2012CB932604); New Drug Discovery Project (2012ZX09506-001-005); the Key Project of Science and Technology Commission of Shanghai Municipality (grants 10JC1410000); and the Shanghai Leading Academic Discipline Project (grant S30203). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.