Longitudinal analysis of healthy colon establishes aspirin as a suppressor of cancer-related epigenetic aging

Clinical Epigenetics

Primo Schär¹  Kaspar Truninger²  Faiza Noreen³  Anna Chaber-Ciopinska⁴  Jaroslaw Regula⁴ 

[1] Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland;Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland;Gastroenterologie Oberaargau, 4900, Langenthal, Switzerland;Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland;Swiss Institute of Bioinformatics, 4053, Basel, Switzerland;Department of Gastroenterology, Medical Center for Postgraduate Education, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland;

关键词: Colon cancer;    Aspirin;    Aging;    DNA methylation;    Epigenetics;   

DOI  :  10.1186/s13148-020-00956-9

来源: Springer

【 摘 要 】

BackgroundColon cancer (CC) is the third most common cancer worldwide, highlighting the importance of developing effective prevention strategies. Accumulating evidence supports that aspirin use reduces CC incidence. We reported previously that aspirin suppresses age-associated and CC-relevant DNA methylation (DNAm) in healthy colon. Here we addressed the aspirin’s effectiveness in longitudinal cohort.MethodsWe measured genome-wide DNAm in 124 healthy normal mucosa samples taken at baseline (time point 1, t1) and after 10-years follow-up (time point 2, t2) from a longitudinal female screening cohort. We investigated the time-dependent methylation drift in aspirin users and nonusers using multivariable regression and related the modulatory effect of aspirin to colonic epigenome-aging and CC.ResultsOver time, compared to nonusers, long-term (≥ 2 years) aspirin users showed less hypermethylated CpGs (proximal: 17% vs. 87%; distal: 16% vs. 70%) and more hypomethylated CpGs (proximal: 83% vs. 13%; distal: 84% vs. 30%). Overall, users showed 2% (P = 0.02) less mean methylation levels than nonusers in proximal colon and displayed repressed methylation age (mAge). Methylation loss in users occurred at several CC-specific tumor suppressors that gained methylation in nonusers. Methylation loss in users effected genes involved in immune system and inflammation, while methylation gain in nonusers effected genes involved in metabolism.ConclusionsThis is the first longitudinal study demonstrating effectiveness of aspirin-use in suppression of age-related and CC-relevant hypermethylation in the normal colon. These findings provide a rationale for future studies to evaluate loci that may serve as markers to identify individuals that will benefit most from aspirin and hence increase its efficiency in CC prevention and therapy.

【 授权许可】

CC BY