HOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type

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. © 2009 The Japan Society of Human Genetics All rights reserved.