Longitudinal analysis of healthy colon establishes aspirin as a suppressor of cancer-related epigenetic aging
- PDF / 4,125,298 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 40 Downloads / 183 Views
Open Access
RESEARCH
Longitudinal analysis of healthy colon establishes aspirin as a suppressor of cancer‑related epigenetic aging Faiza Noreen1,2* , Anna Chaber‑Ciopinska3, Jaroslaw Regula3, Primo Schär1 and Kaspar Truninger1,4*
Abstract Background: Colon 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. Methods: We 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 modu‑ latory effect of aspirin to colonic epigenome-aging and CC. Results: Over 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 inflamma‑ tion, while methylation gain in nonusers effected genes involved in metabolism. Conclusions: This is the first longitudinal study demonstrating effectiveness of aspirin-use in suppression of agerelated 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. Keywords: Colon cancer, Aspirin, Aging, DNA methylation, Epigenetics Background Colon cancer (CC) is the third most common cancer worldwide and the second most common in terms of cancer-related mortality [1]. Age is the strongest risk factor for sporadic CC [2]; however, the risk varies among *Correspondence: [email protected]; k.truninger@gastroenterologie‑oberaargau.ch 1 Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland Full list of author information is available at the end of the article
individuals, even within the same age group, which may reflect heterogeneity in exposure to environmental factor. Indeed, several observational studies have shown that diet and lifestyle are associated with increase CC risk [2–4]. Thus, primary prevention by modification of environmental and lifestyle exposures and the use of chemoprevention are important strategies to reduce further CC incidence. Among chemopreventive ag
Data Loading...
