Background <p>The use of cannabis has been associated with both therapeutic and harmful effects. As with cigarette smoking, cannabis smoking may affect the epigenetic regulation (e.g., DNA methylation) of gene expression which could result in long term health effects. The study of DNA methylation in cannabis smoking has to date been restricted to young adults and there remains yet no evaluation of whether cannabis smoking cessation can reverse epigenetic disturbances. Here, we aimed to investigate the relationship between genome-wide DNA methylation and cannabis smoking.</p> Methods <p>We used peripheral blood from a subset of older adults within the Canadian Cohort of Obstructive Lung Disease (CanCOLD) cohort (<i>n</i> = 93) to conduct an epigenome-wide DNA methylation analysis that identified differential methylated positions (DMPs) associated with cannabis smoking at a false discovery rate &lt; 0.05. Using these DMPs, we then identified differentially methylated genes (DMGs) that enriched pathways associated with both former and current cannabis smoking status.</p> Results <p>We found DMPs corresponding to 12,115 DMGs and 10,806 DMGs that distinguished the current and former cannabis smoking groups, respectively, from the never cannabis smoking group. 5,915 of these DMGs were shared between the current and former cannabis smoking groups. 50 enriched pathways were also shared between the current and former cannabis smoking groups, which were heavily represented by multiple aging- and cancer-related pathways.</p> Conclusions <p>Our findings indicate that in older adults, cannabis smoking is linked with epigenome-wide disruptions, many of which persist despite cannabis smoking cessation. Epigenetic modulation of genes associated with aging and cancer that remains even after quitting cannabis should serve as a caution that there may be long-lasting epigenetic injury with cannabis smoking.</p> Trial registration <p>NCT00920348.</p>

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Cannabis smoking is associated with persistent epigenome-wide disruptions despite smoking cessation

  • Ana I. Hernandez Cordero,
  • Xuan Li,
  • Chen Xi Yang,
  • Amirtha Ambalavanan,
  • Julie L. MacIsaac,
  • Michael S. Kobor,
  • Dany Doiron,
  • Wan Tan,
  • Jean Bourbeau,
  • Don D. Sin,
  • Qingling Duan,
  • Janice M. Leung,
  • Wan C. Tan,
  • JMark FitzGerald,
  • Darcy D. Marciniuk,
  • Denis E. O’Donnell,
  • Paul Hernandez,
  • Kenneth R. Chapman,
  • Brandie Walker,
  • Shawn Aaron,
  • François Maltais,
  • Jonathon Samet,
  • Milo Puhan,
  • Qutayba Hamid,
  • James C. Hogg,
  • Palmina Mancino,
  • Pei Zhi Li,
  • Dennis Jensen,
  • Carolyn Baglole,
  • Yvan Fortier,
  • Wan C. Tan,
  • Don Sin,
  • Julia Yang,
  • Jeremy Road,
  • Joe Comeau,
  • Adrian Png,
  • Kyle Johnson,
  • Harvey Coxson,
  • Jonathon Leipsic,
  • Cameron Hague,
  • Miranda Kirby,
  • Mohsen Sadatsafavi,
  • Teresa To,
  • Andrea Gershon,
  • Wan C. Tan,
  • Harvey Coxson,
  • Pei-Zhi Li,
  • Zhi Song,
  • Andrea Benedetti,
  • Dennis Jensen,
  • Yvan Fortier,
  • Miranda Kirby,
  • Wan C. Tan,
  • Christine Lo,
  • Sarah Cheng,
  • Elena Un,
  • Cynthia Fung,
  • Wen Tiang Wang,
  • Liyun Zheng,
  • Faize Faroon,
  • Olga Radivojevic,
  • Sally Chung,
  • Carl Zou,
  • Palmina Mancino,
  • Jacinthe Baril,
  • Laura Labonte,
  • Kenneth Chapman,
  • Patricia McClean,
  • Nadeen Audisho,
  • Brandie Walker,
  • Curtis Dumonceaux,
  • Lisette Machado,
  • Paul Hernandez,
  • Scott Fulton,
  • Kristen Osterling,
  • Denise Wigerius,
  • Shawn Aaron,
  • Kathy Vandemheen,
  • Gay Pratt,
  • Amanda Bergeron,
  • Denis O’Donnell,
  • Matthew McNeil,
  • Kate Whelan,
  • François Maltais,
  • Cynthia Brouillard,
  • Darcy Marciniuk,
  • Ron Clemens,
  • Janet Baran,
  • Candice Leuschen

摘要

Background

The use of cannabis has been associated with both therapeutic and harmful effects. As with cigarette smoking, cannabis smoking may affect the epigenetic regulation (e.g., DNA methylation) of gene expression which could result in long term health effects. The study of DNA methylation in cannabis smoking has to date been restricted to young adults and there remains yet no evaluation of whether cannabis smoking cessation can reverse epigenetic disturbances. Here, we aimed to investigate the relationship between genome-wide DNA methylation and cannabis smoking.

Methods

We used peripheral blood from a subset of older adults within the Canadian Cohort of Obstructive Lung Disease (CanCOLD) cohort (n = 93) to conduct an epigenome-wide DNA methylation analysis that identified differential methylated positions (DMPs) associated with cannabis smoking at a false discovery rate < 0.05. Using these DMPs, we then identified differentially methylated genes (DMGs) that enriched pathways associated with both former and current cannabis smoking status.

Results

We found DMPs corresponding to 12,115 DMGs and 10,806 DMGs that distinguished the current and former cannabis smoking groups, respectively, from the never cannabis smoking group. 5,915 of these DMGs were shared between the current and former cannabis smoking groups. 50 enriched pathways were also shared between the current and former cannabis smoking groups, which were heavily represented by multiple aging- and cancer-related pathways.

Conclusions

Our findings indicate that in older adults, cannabis smoking is linked with epigenome-wide disruptions, many of which persist despite cannabis smoking cessation. Epigenetic modulation of genes associated with aging and cancer that remains even after quitting cannabis should serve as a caution that there may be long-lasting epigenetic injury with cannabis smoking.

Trial registration

NCT00920348.