Smoking, blood DNA methylation sites and lung cancer risk

Arce Domingo-Relloso; Roby Joehanes; Zulema Rodriguez-Hernandez; Lies Lahousse; Karin Haack; M Daniele Fallin; Miguel Herreros-Martinez; Jason G Umans; Lyle G Best; Tianxiao Huan; Chunyu Liu; Jiantao Ma; Chen Yao; Allan Jerolon; Jose D Bermudez; Shelley A Cole; Dorothy A Rhoades; Daniel Levy; Ana Navas-Acien; Maria Tellez-Plaza

doi:10.1016/j.envpol.2023.122153

Smoking, blood DNA methylation sites and lung cancer risk

Environ Pollut. 2023 Oct 1:334:122153. doi: 10.1016/j.envpol.2023.122153. Epub 2023 Jul 11.

Authors

Arce Domingo-Relloso¹, Roby Joehanes², Zulema Rodriguez-Hernandez³, Lies Lahousse⁴, Karin Haack⁵, M Daniele Fallin⁶, Miguel Herreros-Martinez⁷, Jason G Umans⁸, Lyle G Best⁹, Tianxiao Huan¹⁰, Chunyu Liu¹¹, Jiantao Ma¹², Chen Yao¹³, Allan Jerolon¹⁴, Jose D Bermudez¹⁵, Shelley A Cole⁵, Dorothy A Rhoades¹⁶, Daniel Levy², Ana Navas-Acien¹⁷, Maria Tellez-Plaza³

Affiliations

¹ Integrative Epidemiology Group, Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Carlos III Health Institute, Madrid, Spain; Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA; Department of Statistics and Operations Research, University of Valencia, Spain. Electronic address: [email protected].
² Population Sciences Branch, National Heart, Lung, And Blood Institute, National Institutes of Health, Bethesda, MD, USA; Framingham Heart Study, Framingham, MA, USA.
³ Integrative Epidemiology Group, Department of Chronic Diseases Epidemiology, National Center for Epidemiology, Carlos III Health Institute, Madrid, Spain.
⁴ Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
⁵ Population Health Program, Texas Biomedical Research Institute, San Antonio, TX, USA.
⁶ Department of Mental Health, Johns Hopkins University, Baltimore, USA; Department of Epidemiology, Johns Hopkins University, Baltimore, USA.
⁷ Bioinformatics Unit, Institute for Biomedical Research INCLIVA, Valencia, Spain.
⁸ MedStar Health Research Institute, Washington DC, USA; Georgetown-Howard Universities Center for Clinical and Translational Science, Washington DC, USA.
⁹ Missouri Breaks Industries and Research Inc., Eagle Butte, SD, USA.
¹⁰ Framingham Heart Study, Framingham, MA, USA; University of Massachusetts Medical School, Worcester, MA, USA.
¹¹ Framingham Heart Study, Framingham, MA, USA; Boston University School of Public Health, Boston, MA, USA.
¹² Framingham Heart Study, Framingham, MA, USA; Tufts University Friedman School of Nutrition Science and Policy, Boston, MA, USA.
¹³ Framingham Heart Study, Framingham, MA, USA; Bristol Myers Squibb, Cambridge, MA, USA.
¹⁴ Université Paris Cité, CNRS, MAP5, F-75006, Paris, France.
¹⁵ Department of Statistics and Operations Research, University of Valencia, Spain.
¹⁶ Stephenson Cancer Center, University of Oklahoma Health Sciences Department of Medicine, Oklahoma City, OK, USA.
¹⁷ Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA.

Abstract

Altered DNA methylation (DNAm) might be a biological intermediary in the pathway from smoking to lung cancer. In this study, we investigated the contribution of differential blood DNAm to explain the association between smoking and lung cancer incidence. Blood DNAm was measured in 2321 Strong Heart Study (SHS) participants. Incident lung cancer was assessed as time to event diagnoses. We conducted mediation analysis, including validation with DNAm and paired gene expression data from the Framingham Heart Study (FHS). In the SHS, current versus never smoking and pack-years single-mediator models showed, respectively, 29 and 21 differentially methylated positions (DMPs) for lung cancer with statistically significant mediated effects (14 of 20 available, and five of 14 available, positions, replicated, respectively, in FHS). In FHS, replicated DMPs showed gene expression downregulation largely in trans, and were related to biological pathways in cancer. The multimediator model identified that DMPs annotated to the genes AHRR and IER3 jointly explained a substantial proportion of lung cancer. Thus, the association of smoking with lung cancer was partly explained by differences in baseline blood DNAm at few relevant sites. Experimental studies are needed to confirm the biological role of identified eQTMs and to evaluate potential implications for early detection and control of lung cancer.

Keywords: DNA methylation; Framingham heart study; Lung cancer incidence; Smoking; Strong heart study.

MeSH terms

Base Sequence
DNA Methylation*
Epigenesis, Genetic
Humans
Lung Neoplasms* / epidemiology
Lung Neoplasms* / genetics
Smoking / epidemiology
Tobacco Smoking / genetics

Abstract

MeSH terms

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