Association between nutrient intake related to the one-carbon metabolism and colorectal cancer risk: a case-control study in the Basque Country.

PURPOSE: Epidemiologic evidence for the association between methyl-donor nutrient intake and colorectal cancer (CRC) risk remains inconclusive. We aimed to examine the relationship between intake of vitamins of the B group, methionine, total choline and betaine and CRC risk, in a population from the CRC screening programme in the Basque Country. DESIGN: This observational study included 308 patients with CRC and 308 age- and sex-matched subjects as controls. During recruitment, dietary, anthropometric, lifestyle, socioeconomic, demographic, and health status information was collected. Conditional logistic regression was used to estimate the odds ratios (ORs) for CRC risk. RESULTS: The adjusted ORs for CRC risk decreased with higher intakes of choline and betaine (p < 0.05). After further adjustment for folate, high intake of choline and betaine remained associated with a reduced CRC risk (adjusted model for choline, OR third tertile vs first tertile = 0.45, 95% CI 0.26-0.80, p = 0.006; for betaine, OR third tertile vs first tertile = 0.27, 95% CI 0.16-0.47, p < 0.001). Regarding the other nutrients, our findings indicated a non-significant decrease in CRC risk with the high level of intake. CONCLUSIONS: Our data suggest that choline and betaine intake influence CRC risk in the studied population.

Influence of methyl donor nutrients as epigenetic regulators in colorectal cancer: A systematic review of observational studies.

BACKGROUND: Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear. AIM: To improve the current understanding of the molecular basis of CRC. METHODS: A literature search in the Medline database, Reference Citation Analysis (https:// www.referencecitationanalysis.com/), and manual reference screening were performed to identify observational studies published from inception to May 2022. RESULTS: A total of fourteen case-control studies and five cohort studies were identified. These studies included information on dietary methyl donors, dietary components that potentially modulate the bioavailability of methyl groups, genetic variants of methyl metabolizing enzymes, and/or markers of CpG island methylator phenotype and/or microsatellite instability, and their possible interactions on CRC risk. CONCLUSION: Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms, methyl donor nutrients (such as folate) and alcohol on CRC risk. Moreover, vitamin B6, niacin, and alcohol may affect CRC risk through not only genetic but also epigenetic regulation. Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.