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

// Hualong Qin 1, * , Jianjie Zhu 2, 3, * , Yuanyuan Zeng 2, 3, * , Wenwen Du 2 , Dan Shen 2 , Zhe Lei 4 , Qian Qian 5 , Jian-an Huang 2, 3 , Zeyi Liu 2, 3 1 Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China 2 Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China 3 Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China 4 Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou 215123, China 5 Division of Allergy & Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA * These authors have contributed equally to this work Correspondence to: Zeyi Liu, email: liuzeyisuda@163.com Jian-an Huang, email: huang_jian_an@yeah.net Keywords: non-small cell lung cancer, base excision repair, hOGG1, SNP, methylation Received: August 31, 2016     Accepted: November 22, 2016     Published: December 26, 2016 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.