Lourdes Pilar Chávez-Hidalgo, Silvia Martín-Fernández-de-Labastida, Marian M de Pancorbo, Marta Arroyo-Izaga
Journal: World journal of gastroenterology 2023;29(7):1219-1234
PMID: 36926668
Colorectal cancer (CRC) is the third most frequent type of cancer and yet has the second highest mortality rate in cancer patients worldwide. Hence there is an urgency to understand more about dietary and lifestyle factors that can help to prevent this type of cancer. It is known that folate has a preventive function in CRC, possibly due to its role in DNA methylation. Methylation is the addition of methyl groups to DNA, which influences gene expression and regulation. This systematic review investigated how folate and other dietary methyl groups and methyl influencers such as B vitamins and alcohol influence the development of CRC, whilst also considering various genetic variants in methyl-metabolising enzymes (polymorphisms). The analysis included a total of 19 case-control and cohort studies and highlighted that potential interactions between methyl donor nutrients, genetic variants, and alcohol influence CRC risk. For most, high levels of folate intake were considered a protective factor, while high alcohol consumption proved to be a risk factor. Yet these interactions appear to be complex, with gender, genetic variations and folate status appearing to contribute to variable and, in some cases, contradictory outcomes. The authors suggested in their findings that Vitamin B6, Vitamin B3 (Niacin), and alcohol may affect CRC by influencing its risk by acting on both the genetic code itself and the epigenetic factors that control gene activity. Further research is needed to better understand the complexity of these mechanisms, and to help clarify the influence of methyl group donors as epigenetic regulators of gene activity in CRC development.
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, (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 B, 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.
©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
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