Lee Do-Hoon, Hwang Sang-Hyun, Lim Min Kyung, Oh Jin-Kyoung, Song Da Young, Yun E Hwa, Park Eun Young
Department of Laboratory Medicine, Center for Diagnostic Oncology, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeinggi-do, Republic of Korea.
Hematologic Malignancy Branch, Research Institute and Hospital, National Cancer Center, Goyang-si, Gyeinggi-do, Republic of Korea.
PLoS One. 2017 Apr 28;12(4):e0176783. doi: 10.1371/journal.pone.0176783. eCollection 2017.
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.
越来越多的证据表明吸烟与DNA甲基化之间存在关联。因此，DNA甲基化现在被认为是吸烟暴露的一个有前景的生物标志物。我们评估了甲基化标志物（芳烃受体（AHRR）和凝血因子Ⅱ受体样3（F2RL3））与尿可替宁以及自我报告的吸烟状况之间的关系。对330名成年人（46至87岁）测量了血液中AHRR和F2RL3的DNA甲基化水平以及尿可替宁。采用焦磷酸测序法测量与吸烟暴露相关的AHRR和F2RL3的DNA甲基化。使用逻辑回归分析来分析与DNA甲基化和尿可替宁相关的肺癌风险。与从不吸烟的个体相比，当前吸烟者的AHRR和F2RL3基因显著低甲基化。观察到尿可替宁与甲基化水平之间呈负相关。AHRR和F2RL3的甲基化能高精度地区分当前吸烟者和从不吸烟者。逻辑多变量分析表明，AHRR甲基化与肺癌风险显著相关（比值比（OR）=0.96，P=0.011）。我们的研究验证了在一个韩国人群队列中报告的与吸烟相关的DNA甲基化标志物。总之，AHRR和F2RL3的DNA甲基化为吸烟暴露提供了准确的测量方法。反映吸烟对肺癌风险长期影响的甲基化标志物在区分既往吸烟者和从不吸烟者方面表现更佳。
