Systematic Reviews
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2023; 29(7): 1219-1234
Published online Feb 21, 2023. doi: 10.3748/wjg.v29.i7.1219
Influence of methyl donor nutrients as epigenetic regulators in colorectal cancer: A systematic review of observational studies
Lourdes Pilar Chávez-Hidalgo, Silvia Martín-Fernández-de-Labastida, Marian M de Pancorbo, Marta Arroyo-Izaga
Lourdes Pilar Chávez-Hidalgo, Silvia Martín-Fernández-de-Labastida, Marta Arroyo-Izaga, Department of Pharmacy and Food Sciences, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz 01006, Araba/Álava, Spain
Marian M de Pancorbo, Department of Z. and Cellular Biology A., University of the Basque Country UPV/EHU, Vitoria-Gasteiz 01006, Araba/Álava, Spain
Marian M de Pancorbo, Marta Arroyo-Izaga, BIOMICs Research Group, MICROFLUIDICs and BIOMICs Cluster UPV/EHU, Lascaray Research Center, University of the Basque Country UPV/EHU, Vitoria-Gasteiz 01006, Araba/Álava, Spain
Author contributions: The study was conceived and designed by Chávez-Hidalgo LP, Martín-Fernández-de-Labastida S, M de Pancorbo M, and Arroyo-Izaga M; The data were acquired, collated, and analysed by Chávez-Hidalgo LP and Arroyo-Izaga M; The study was drafted and revised critically for important intellectual content by all authors; The work reported in the paper has been performed by the authors, unless clearly specified in the text; All authors gave final approval of the version to be published and have contributed to the study; No ethical approval was needed.
Supported by The Basque Government (BIOMICs Research Group, MICROFLUIDICs & BIOMICs Cluster of the University of the Basque Country UPV/EHU), No. IT1633-22.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marta Arroyo-Izaga, PharmD, Department of Pharmacy and Food Sciences, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad, No. 7, Vitoria-Gasteiz 01006, Araba/Álava, Spain. marta.arroyo@ehu.eus
Received: September 28, 2022
Peer-review started: September 28, 2022
First decision: December 12, 2022
Revised: December 26, 2022
Accepted: February 13, 2023
Article in press: February 13, 2023
Published online: February 21, 2023
Abstract
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.

Keywords: Colorectal cancer, DNA methylation, Epigenetics, Methyl donors, Microsatellite instability, Nutrients

Core Tip: Dietary methyl donors might influence DNA methylation during the carcinogenesis of colorectal cancer (CRC). However, whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear. We conducted a systematic review on this topic to improve the current understanding of the molecular basis of CRC. 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.