Performance of urine cotinine and hypomethylation of AHRR and F2RL3 as biomarkers for smoking exposure in a population-based cohort

• Published in: PloS one Vol. 12; no. 4; p. e0176783
• Main Authors: Lee, Do-Hoon, Hwang, Sang-Hyun, Lim, Min Kyung, Oh, Jin-Kyoung, Song, Da Young, Yun, E Hwa, Park, Eun Young
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-04-2017; Public Library of Science (PLoS)
• Subjects: Adults; Aged; Aged, 80 and over; Area Under Curve; Basic Helix-Loop-Helix Transcription Factors - blood; Basic Helix-Loop-Helix Transcription Factors - genetics; Biological markers; Biology and life sciences; Biomarkers; Biomarkers - blood; Biomarkers - urine; Cancer; Cotinine; Cotinine - urine; Deoxyribonucleic acid; Disease; Disease prevention; DNA; DNA Methylation; Exposure; Female; Gene expression; Genetic testing; Genetics; Genomes; Health risk assessment; Health risks; Hospitals; Humans; Hydrocarbons; Laboratories; Logistic Models; Lung cancer; Lung diseases; Lung Neoplasms - blood; Lung Neoplasms - epidemiology; Lung Neoplasms - genetics; Lung Neoplasms - urine; Male; Medical research; Medicine; Medicine and Health Sciences; Methylation; Middle Aged; Multivariate Analysis; Physical Sciences; Physiology; Population; Prospective Studies; Receptors, Thrombin - blood; Receptors, Thrombin - genetics; Regression analysis; Repressor Proteins - blood; Repressor Proteins - genetics; Republic of Korea - epidemiology; Risk; Risk factors; ROC Curve; Self Report; Smoking; Smoking - blood; Smoking - epidemiology; Smoking - genetics; Smoking - urine; Studies; Tobacco; Urine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0176783

There is a growing body of evidence demonstrating an association between smoking and DNA methylation. Accordingly, DNA methylation is now considered a promising biomarker of smoking exposure. We evaluated the relationship between methylation markers (AHRR and F2RL3) and urine cotinine as well as self-reported smoking status. DNA methylation levels of AHRR and F2RL3 in blood as well as urine cotinine were measured in 330 adults (46 to 87 years of age). Pyrosequencing was performed to measure DNA methylation of AHRR and F2RL3 associated with smoking exposure. The lung cancer risk associated with DNA methylation and urine cotinine was analyzed using logistic regression analysis. The AHRR and F2RL3 genes were significantly hypomethylated in current smokers compared to in individuals who have never smoked. An inverse relationship was observed between urine cotinine and methylation levels. Methylation of AHRR and F2RL3 distinguished current smokers from never-smokers with high accuracy. Logistic multivariate analysis showed that AHRR methylation is significantly associated with the risk of lung cancer (OR = 0.96, P = 0.011). Our study validated the smoking-associated DNA methylation markers reported in a Korean population-based cohort. In conclusion, DNA methylation of AHRR and F2RL3 provided accurate measures for smoking exposure. Methylation markers reflecting the long-term effect of smoking on the risk of lung cancer showed better performance in distinguishing former smokers from never-smokers.