1. Non-cigarette tobacco products, aryl-hydrocarbon receptor repressor gene methylation and smoking-related health outcomes.
- Author
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Eckhardt CM, Balte P, Morris JE, Bhatt SP, Couper D, Fetterman J, Freedman N, Jacobs DR, Hou L, Kalhan R, Liu Y, Loehr L, Lutsey PL, Schwartz JE, White W, Yende S, London SJ, Sanchez TR, and Oelsner EC
- Subjects
- Humans, Female, Male, Middle Aged, Repressor Proteins genetics, Basic Helix-Loop-Helix Transcription Factors genetics, Aged, Smoking adverse effects, Smoking epidemiology, United States epidemiology, Adult, DNA Methylation
- Abstract
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., Competing Interests: Competing interests: SPB has had consultancy agreements with Boehringer Ingelheim, Sanofi/Regeneron and IntegrityCE. He has participated in research with Nuvaira Sanofi for which his institution has been remunerated. RK has had consultancy agreements with CVS Caremark, AstraZeneca, GlaxoSmithKline and Boehringer Ingelheim. He has participated in research with AstraZeneca, PneumRx/BTG and Spiration, for which his institution has been remunerated., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
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