Aberrant promoter methylation of hOGG1 may be associated with increased risk of non-small cell lung cancer

Abstract

DNA methylation may epigenetically inactivate tumor suppressor genes in NSCLC. As the human 8-oxoguanine DNA glycosylase (hOGG1) gene promoter is frequently methylated in NSCLC, we evaluated whether genetic or epigenetic alterations of hOGG1 are associated with increased risk of non-small cell lung cancer. Three hOGG1 haplotype-tagging SNPs (htSNP) were genotyped in PCR-restriction fragment length polymorphism assays, and one htSNP was genotyped in a PCR-single-strand conformation polymorphism assay in case-control studies of 217 NSCLC patients and 226 healthy controls. The methylation profiles of peripheral blood mononuclear cell specimens from 121 NSCLC patients and 121 controls were determined through methylation-specific PCR of hOGG1. No differences in allele or genotype frequencies between NSCLC patients and controls were observed at any of the four polymorphic sites (rs159153, rs125701, rs1052133, and rs293795). However, hOGG1 methylation-positive carriers had a 2.25-fold greater risk of developing NSCLC (adjusted odds ratio: 2.247; 95% confidence interval: 1.067-4.734; P = 0.03) than methylation-free subjects. Furthermore, the demethylating agent 5-aza-2’-deoxycytidine restored hOGG1 expression in NSCLC cell lines. These data provide strong evidence of an association between peripheral blood mononuclear cell hOGG1 methylation and the risk of NSCLC in a Chinese population.