Comprehensive assessment of associations between ERCC2 Lys751Gln/Asp312Asn polymorphisms and risk of non- Hodgkin lymphoma

Asian Pac J Cancer Prev. 2014;15(21):9347-53. doi: 10.7314/apjcp.2014.15.21.9347.

Abstract

Background: Excision repair crossing-complementing group 2 (ERCC2), also called xeroderma pigmentosum complementary group D (XPD), plays a crucial role in the nucleotide excision repair (NER) pathway. Previous epidemiological studies have reported associations between ERCC2 polymorphisms and non-Hodgkin lymphoma (NHL) risk, but the results have remained controversial.

Materials and methods: We conducted this meta- analysis based on eligible case-control studies to investigate the role of two ERCC2 polymorphisms (Lys751Gln and Asp312Asn) in determining susceptibility to NHL. Ten case-control studies from several electronic databases were included in our study up to August 14, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models to estimate the association strength.

Results: The combined results based on all studies did not show any association between Lys751Gln/Asp312Asn polymorphisms and NHL risk for all genetic models. Stratified analyses by histological subtype and ethnicity did not indicate any significant association between Lys751Gln polymorphism and NHL risk. However, a significant reduced risk of NHL was found among population-based studies (Lys/Gln versus Lys/Lys: OR=0.87, 95% CI=0.77-0.99, P=0.037) but not hospital-based studies. As for Asp312Asn polymorphism, there was no evidence for the association between this polymorphism and the risk of NHL in all subgroup analyses.

Conclusions: This meta-analysis suggests that there may be no association between Lys751Gln/Asp312Asn polymorphism and the risk of NHL and its two subtypes, whereas ERCC2 Lys751Gln heterozygote genotype may provide protective effects against the risk of NHL in population-based studies. Therefore, large-scale and well-designed studies are needed to clarify the effects of haplotypes, gene-gene, and gene-environment interactions on these polymorphisms and the risk of NHL and its different histological subtypes in an ethnicity specific population.

Publication types

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

MeSH terms

  • Asian People / genetics
  • Case-Control Studies
  • Confidence Intervals
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Humans
  • Incidence
  • Lymphoma, Non-Hodgkin / ethnology*
  • Lymphoma, Non-Hodgkin / genetics*
  • Male
  • Odds Ratio
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Risk Assessment
  • White People / genetics
  • Xeroderma Pigmentosum Group D Protein / genetics*

Substances

  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human