ArticleJournal of the National Cancer Institute2019
COMT and Alpha-Tocopherol Effects in Cancer Prevention: Gene-Supplement Interactions in Two Randomized Clinical Trials.
Article in Journal of the National Cancer Institute, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
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Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Personalization matters: the effect of sex in multivitamin-multimineral-based cancer prevention.GeroScience · 2024Pooled it
- Vitamin D and Multiple Health Outcomes: An Umbrella Review of Observational Studies, Randomized Controlled Trials, and Mendelian Randomization Studies.Advances in nutrition (Bethesda, Md.) · 2022Pooled it
- Pharmacogenomics and Placebo Response in a Randomized Clinical Trial in Asthma.Clinical pharmacology and therapeutics · 2019Trial
- Enterococcus-driven metabolite-host gene networks in IBD-associated colorectal carcinogenesis: integrative multi-omics and experimental validation.Frontiers in cell and developmental biology · 2026Article
- The Role of Dietary Vitamins and Antioxidants in Preventing Colorectal Cancer: A Systematic Review.Cureus · 2024Review
- Telomerase Inhibition in the Treatment of Leukemia: A Comprehensive Review.Antioxidants (Basel, Switzerland) · 2024Review
- Relationship between food-derived antioxidant vitamin intake and breast cancer risk: a mendelian randomized study.European journal of nutrition · 2023Article
- Review
- Interaction between vitamin E intake and a COMT gene variant on colorectal cancer risk among Korean adults: a case-control study.Epidemiology and health · 2023Article
- Identification of a prognosis-related ceRNA network in cholangiocarcinoma and potentially therapeutic molecules using a bioinformatic approach and molecular docking.Scientific reports · 2022Article
- Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1.Cancer discovery · 2022Article
- Genomic Effects Associated With Response to Placebo Treatment in a Randomized Trial of Irritable Bowel Syndrome.Frontiers in pain research (Lausanne, Switzerland) · 2021Article
- Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review.Frontiers in medicine · 2021Review
- Obesity in Postmenopausal Breast Cancer Patients: It Is Time to Improve Actions for a Healthier Lifestyle. The Results of a Comparison Between Two Italian Regions With Different "Presumed" Lifestyles.Frontiers in oncology · 2021Article
- Catechol-O-Methyltransferase and Cardiovascular Disease: MESA.Journal of the American Heart Association · 2019Observational
- Drug-Placebo Additivity in Randomized Clinical Trials.Clinical pharmacology and therapeutics · 2019Article
- Systems pharmacogenomics - gene, disease, drug and placebo interactions: a case study in COMT.Pharmacogenomics · 2019Article
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13 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundVitamins are among the most frequently used supplements (48% of US adults). However, little is known about contributions of genetic variation to their efficacy and safety. Multiple pathways link catechol-O-methyltransferase (COMT) to the vitamin E supplement, alpha-tocopherol, and cancer.
methodsHere we determined if COMT exerted pharmacogenetic effects on cancer prevention in two randomized trials of alpha-tocopherol supplementation. Pharmacogenetic effects of common COMT rs4680 (val158met), which encodes a nonsynonymous valine-to-methionine substitution, were examined in the trial plus a 10-year post-trial follow-up (overall) period of The Women's Genome Health Study (WGHS, N = 23 294), a 10-year alpha-tocopherol and aspirin trial with 10 years post-trial follow-up. Results were validated in a case/control (N = 2396/2235) subset of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC, N = 29 133). The primary outcome was total cancers. Rates of cancer types prevalent in women (colorectal, breast, lung, uterine, and lymphoma/leukemia) were also examined. All statistical tests were two-sided.
resultsRandom-effects meta-analysis of rs4680 genotype strata, in WGHS and ATBC overall periods, revealed differential alpha-tocopherol effects compared with placebo: met/met (hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.80 to 0.97; P = .01), val/met (HR = 0.99; 95% CI = 0.92 to 1.06; P = .74), and val/val (HR = 1.18; 95% CI = 1.06 to 1.31; P = .002) with a statistically significant COMT by alpha-tocopherol interaction (Pinteraction <.001). Timing of effects differed, with stronger effects in WGHS trial and ATBC post-trial.
conclusionPharmacogenetic analysis of COMT and cancer prevention in two large randomized trials revealed statistically significant COMT by alpha-tocopherol interaction, such that alpha-tocopherol was beneficial among rs4680 met-allele (28.0%), but not val-allele (22.8%) homozygotes. These effects indicate the need for additional studies of genetic variation as a determinant of the benefits and possible harms of over-the-counter supplements, like alpha-tocopherol, used for health promotion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.