Introduction Cigarette smoking leads to altered DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) gene. However, it remains unknown whether pipe or cigar smoking is associated with AHRR methylation. We evaluated associations of non-cigarette tobacco use with AHRR methylation and determined if AHRR methylation was associated with smoking-related health outcomes. Methods Data were pooled across four population-based cohorts that enrolled participants from 1985 to 2002. Tobacco exposures were evaluated using smoking questionnaires. AHRR cg05575921 methylation was measured in peripheral blood leucocyte DNA. Spirometry and respiratory symptoms were evaluated at the time of methylation measurements and in subsequent visits. Vital status was monitored using the National Death Index. Results Among 8252 adults (mean age 56.7±10.3 years, 58.1% women, 40.6% black), 4857 (58.9%) participants used cigarettes and 634 (7.7%) used non-cigarette tobacco products. Exclusive use of non-cigarette tobacco products was independently associated with lower AHRR methylation (−2.44 units, 95% CI −4.42 to −0.45), though to a lesser extent than exclusive use of cigarettes (−6.01 units, 95% CI −6.01 to −4.10). Among participants who exclusively used non-cigarette tobacco products, reduced AHRR methylation was associated with increased respiratory symptom burden (OR 1.60, 95% CI 1.03 to 2.68) and higher all-cause mortality (log-rank p=0.02). Conclusion Pipe and cigar smoking were independently associated with lower AHRR methylation in a multiethnic cohort of US adults. Among users of non-cigarette tobacco products, lower AHRR methylation was associated with poor respiratory health outcomes and increased mortality. AHRR methylation may identify non-cigarette tobacco users with an increased risk of adverse smoking-related health outcomes. Data are available on reasonable request.

中文翻译：

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非卷烟烟草制品、芳烃受体抑制基因甲基化和吸烟相关健康结局


简介 吸烟导致芳烃受体抑制物 （AHRR） 基因的 DNA 甲基化改变。然而，目前尚不清楚烟斗或雪茄吸烟是否与 AHRR 甲基化有关。我们评估了非香烟烟草使用与 AHRR 甲基化的关联，并确定 AHRR 甲基化是否与吸烟相关的健康结局相关。方法 数据汇总了 1985 年至 2002 年招募参与者的四个基于人群的队列。使用吸烟问卷评估烟草暴露。在外周血白细胞 DNA 中测量 AHRR cg05575921 甲基化。在甲基化测量时和随后的就诊中评估肺活量测定和呼吸道症状。使用国家死亡指数监测生命状态。结果 在 8252 名成年人 （平均年龄 56.7±10.3 岁，58.1% 为女性，40.6% 为黑人）中，4857 名 （58.9%） 参与者使用香烟，634 名 （7.7%） 使用非卷烟烟草产品。仅使用非卷烟烟草制品与较低的 AHRR 甲基化独立相关（-2.44 个单位，95% CI -4.42 至 -0.45），尽管程度低于纯香烟（-6.01 个单位，95% CI -6.01 至 -4.10）。在仅使用非香烟烟草制品的参与者中，AHRR 甲基化降低与呼吸系统症状负担增加相关 （OR 1.60,95% CI 1.03 至 2.68） 和较高的全因死亡率 （log-rank p=0.02）。结论 在美国成年人的多种族队列中，吸烟烟斗和雪茄与较低的 AHRR 甲基化独立相关。在非香烟烟草制品的使用者中，较低的 AHRR 甲基化与不良的呼吸健康结局和死亡率增加有关。 AHRR 甲基化可以识别非卷烟烟草使用者发生与吸烟相关的不良健康结局的风险增加。数据可应合理要求提供。