The association between OGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis of 27 studies

PLoS One. 2012;7(4):e35970. doi: 10.1371/journal.pone.0035970. Epub 2012 Apr 23.

Abstract

Background: Numerous studies have investigated association of OGG1 Ser326Cys polymorphism with lung cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 27 publications encompass 9663 cases and 11348 controls to comprehensively evaluate such associations.

Methods: We searched publications from MEDLINE and EMBASE which were assessing the associations between OGG1 Ser326Cys polymorphism and lung cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We used genotype based mRNA expression data from HapMap for SNP rs1052133 in normal cell lines among 270 subjects with four different ethnicities.

Results: The results showed that individuals carrying the Cys/Cys genotype did not have significantly increased risk for lung cancer (OR = 1.15, 95% CI = 0.98-1.36) when compared with the Ser/Ser genotype; similarly, no significant association was found in recessive, dominant or heterozygous co-dominant model (Ser/Cys vs. Cys/Cys). However, markedly increased risks were found in relatively large sample size (Ser/Ser vs. Cys/Cys: OR = 1.29, 95% CI = 1.13-1.48, and recessive model: OR = 1.19, 95% CI = 1.07-1.32). As to histological types, we found the Cys/Cys was associated with adenocarcinoma risk (Ser/Ser vs. Cys/Cys: OR = 1.32, 95% CI = 1.12-1.56; Ser/Cys vs. Cys/Cys: OR = 1.19, 95% CI = 1.04-1.37, and recessive model OR = 1.23, 95% CI = 1.08-1.40). No significant difference of OGG1 mRNA expression was found among genotypes between different ethnicities.

Conclusions: Despite some limitations, this meta-analysis established solid statistical evidence for an association between the OGG1 Cys/Cys genotype and lung cancer risk, particularly for studies with large sample size and adenocarcinoma, but this association warrants additional validation in larger and well designed studies.

Publication types

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

MeSH terms

  • Amino Acid Substitution
  • DNA Glycosylases / genetics*
  • DNA Glycosylases / metabolism
  • Databases, Genetic
  • Genetic Predisposition to Disease*
  • Genotype
  • HapMap Project
  • Humans
  • Lung Neoplasms / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • RNA, Messenger / metabolism
  • Risk Factors

Substances

  • RNA, Messenger
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human