title: 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.
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Hualong
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Shen
authors.affiliation: Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou 215123, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Division of Allergy & Immunology, Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qian
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China.
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Huang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.|Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China.
authors.forename: Zeyi
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000072283:A549 Cells; D000368:Aged; D044466:Asian People / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D045647:DNA Glycosylases / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D000077209:Decitabine; D015254:DNA Modification Methylases; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D001374:Azacitidine
keywords: SNP; base excision repair; hOGG1; methylation; non-small cell lung cancer