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、芳基烃受体阻遏基因甲基化和吸烟相关的健康结果


简介 吸烟会导致芳基烃受体阻遏物 (AHRR) 基因的 DNA 甲基化发生改变。然而，目前尚不清楚吸烟斗或雪茄是否与 AHRR 甲基化有关。我们评估了非卷烟烟草使用与 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果相关。方法 汇集 1985 年至 2002 年期间纳入参与者的四个基于人群的队列的数据。使用吸烟问卷评估烟草暴露情况。测量外周血白细胞 DNA 中的 AHRR cg05575921 甲基化。在甲基化测量时和随后的访视中评估肺量测定和呼吸道症状。使用国家死亡指数监测生命状况。结果 在 8252 名成年人（平均年龄 56.7±10.3 岁，58.1% 女性，40.6% 黑人）中，4857 名参与者（58.9%）使用卷烟，634 名参与者（7.7%）使用非卷烟烟草制品。单独使用非卷烟烟草产品与较低的 AHRR 甲基化独立相关（-2.44 单位，95%CI -4.42 至 -0.45），但程度低于单独使用香烟（-6.01 单位，95%CI -6.01）至-4.10）。在只使用非卷烟烟草产品的参与者中，AHRR 甲基化降低与呼吸道症状负担增加（OR 1.60，95%CI 1.03 至 2.68）和更高的全因死亡率相关（对数秩 p=0.02）。结论 在美国多种族成年人队列中，吸烟斗和雪茄与较低的 AHRR 甲基化独立相关。在非卷烟烟草产品的使用者中，较低的 AHRR 甲基化与呼吸系统健康状况不佳和死亡率增加有关。 AHRR 甲基化可能会识别非卷烟烟草使用者与吸烟相关的不良健康结果的风险增加。可根据合理要求提供数据。