hOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type

J Hum Genet. 2009 Dec;54(12):739-45. doi: 10.1038/jhg.2009.108. Epub 2009 Oct 30.

Abstract

Human 8-oxoguanine DNA glycosylase 1 (hOGG1) has a major role in the repair of 8-hydroxyguanine, a major promutagenic DNA lesion. The genetic polymorphism rs1052133, which leads to substitution of the amino acid at codon 326 from Ser to Cys, shows functional differences, namely a decrease in enzyme activity in hOGG1-Cys326. Although several studies have investigated the association between rs1052133 and lung cancer susceptibility, the effect of this locus on lung cancer according to histology remains unclear. We therefore conducted a case-control study with 515 incident lung cancer cases and 1030 age- and sex-matched controls without cancer, and further conducted a meta-analysis. In overall analysis, the homozygous Cys/Cys genotype showed a significant association with lung cancer compared to Ser allele carrier status (odds ratio (OR)=1.31, 95% confidence interval (CI)=1.02-1.69). By histology-based analysis, the Cys/Cys genotype showed a significantly positive association with small-cell carcinoma (OR=2.40, 95% CI=1.32-4.49) and marginally significant association with adenocarcinoma (OR=1.32, 95% CI=0.98-1.77). A meta-analysis of previous and our present study revealed that this polymorphism is positively associated with adenocarcinoma, although suggestive associations were also found for squamous- and small-cell lung cancers. These results indicate that rs1052133 contributes to the risk of adenocarcinoma of lung.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Carcinoma, Small Cell / genetics*
  • Carcinoma, Small Cell / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Cysteine / genetics
  • DNA Glycosylases / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Multivariate Analysis
  • Mutation, Missense
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Serine / genetics
  • Smoking

Substances

  • Serine
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human
  • Cysteine