ArticleJournal of the National Cancer Institute2014
Modulation of age- and cancer-associated DNA methylation change in the healthy colon by aspirin and lifestyle.
Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Global differences in the prevalence of the CpG island methylator phenotype of colorectal cancer.BMC cancer · 2019Pooled it
- Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention.Cancer prevention research (Philadelphia, Pa.) · 2025Trial
- Impact of Maternal Aspirin Therapy on Neonatal Epigenetic Patterns.American journal of perinatology · 2026Article
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- Colonic Aging and Colorectal Cancer: An Unignorable Interplay and Its Translational Implications.Biology · 2025Review
- Cellular stress and epigenetic regulation in adult stem cells.Life science alliance · 2024Review
- DNA-methylation variability in normal mucosa: a field cancerization marker in patients with adenomatous polyps.Journal of the National Cancer Institute · 2024Article
- DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine.Exploration of targeted anti-tumor therapy · 2024Review
- Diesel Exhaust Particle (DEP)-induced glucose intolerance is driven by an intestinal innate immune response and NLRP3 activation in mice.Particle and fibre toxicology · 2023Article
- Disentangling tumorigenesis-associated DNA methylation changes in colorectal tissues from those associated with ageing.Epigenetics · 2022Article
- Molecular Biologic and Epidemiologic Insights for Preventability of Colorectal Cancer.Journal of the National Cancer Institute · 2022Article
- Caloric restriction induced epigenetic effects on aging.Frontiers in cell and developmental biology · 2022Review
- The association betweenFrontiers in cardiovascular medicine · 2022Article
- CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer.Frontiers in oncology · 2022Article
- Article
- DNA methylation signatures to predict the cervicovaginal microbiome status.Clinical epigenetics · 2020Article
- Prevention in the age of personal responsibility: epigenetic risk-predictive screening for female cancers as a case study.Journal of medical ethics · 2020Article
- Longitudinal analysis of healthy colon establishes aspirin as a suppressor of cancer-related epigenetic aging.Clinical epigenetics · 2020Observational
- Non-Surgical Cancer Risk Reduction inCancers · 2020Article
- COVID-19: A Challenge to Physiology of Aging.Frontiers in physiology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAberrant DNA methylation in gene promoters is associated with aging and cancer, but the circumstances determining methylation change are unknown. We investigated the impact of lifestyle modulators of colorectal cancer (CRC) risk on the stability of gene promoter methylation in the colonic mucosa.
methodsWe measured genome-wide promoter CpG methylation in normal colon biopsies (n = 1092) from a female screening cohort, investigated the interaction of lifestyle factors with age-dependent increase in methylation with log-linear multivariable regression, and related their modifying effect to hypermethylation in CRC. All statistical tests were two-sided.
resultsOf 20025 promoter-associated CpGs analyzed, 1713 showed statistically significant age-dependent methylation gains. Fewer CpGs acquired methylation in users of aspirin (≥ 2 years) and hormonal replacement therapy (HRT age ≥ 50 years) compared with nonusers (43 vs 1355; 1 vs1377, respectively), whereas more CpGs were affected in smokers (≥ 20 years) and individuals with a body mass index (BMI) of 25 kg/m(2) and greater compared with control groups (180 vs 39; 554 vs 144, respectively). Fifty percent of the CpGs showing age-dependent methylation were found hypermethylated in CRC (odds ratio [OR] = 20; 95% confidence interval [CI] = 18 to 23; P < 2 × 10(-16)). These loci gained methylation with a higher median rate compared with age-only methylated sites (P = 2 × 10(-76)) and were enriched for polycomb regions (OR = 3.67). Importantly, aspirin (P < .001) and HRT use (P < .001) reduced the methylation rate at these cancer-related genes, whereas smoking (P < .001) and high BMI (P = .004) increased it.
conclusionsLifestyle, including aspirin use, modulates age-associated DNA methylation change in the colonic epithelium and thereby impacts the evolution of cancer methylomes.
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