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Role of Folate in Colon Cancer Development and Progression
Open accessAbstract
Folate, a water-soluble B vitamin and important cofactor in 1-carbon transfer, is an important nutritional factor that may modulate the development of colorectal cancer. Epidemiologic and clinical studies indicate that dietary folate intake and blood folate levels are inversely associated with colorectal cancer risk. Collectively, these studies suggest an approximately 40% reduction in the risk of colorectal cancer in individuals with the highest dietary folate intake compared with those with the lowest intake. Animal studies using chemical and genetically predisposed rodent models have provided considerable support for a causal relationship between folate depletion and colorectal carcinogenesis as well as a dose-dependent protective effect of folate supplementation. However, animal studies have also shown that the dose and timing of folate intervention are critical in providing safe and effective chemoprevention; exceptionally high supplemental folate levels and folate intervention after microscopic neoplastic foci are established in the colorectal mucosa promote rather than suppress colorectal carcinogenesis. These animal studies in conjunction with clinical observations suggest that folate possesses the dual modulatory effects on carcinogenesis depending on the timing and dose of folate intervention. Folate deficiency has an inhibitory effect whereas folate supplementation has a promoting effect on progression of established neoplasms. In contrast, folate deficiency in normal epithelial tissues appears to predispose them to neoplastic transformation, and modest levels of folate supplementation suppress the development of tumors in normal tissues. Notwithstanding the limitations associated with animal models, these animal studies suggest that the optimal timing and dose of folate intervention need to be established for safe and effective chemoprevention in humans.
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“This means that although MR has been a powerful tool for confirming or discovering factors that cause disease, it does not often identify therapeutic targets.185”
From Mendelian randomization (2022) · cites this paper as [185]
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“Importantly, case-only study designs may be severely compromised by collider bias[[G] 56,64, which must be taken into account in data analysis185.”
From Mendelian randomization (2022) · cites this paper as [185]
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Metadata
- Authors
- Kim, Y.-I.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Kim, Young-In
- ORCID
- Kim, Young-In
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 133
- Issue
- 11
- Pages
- 3731S-3739S
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2097612130
- Cited by
- 386
- References
- 102
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 7 · 2023: 18 · 2022: 10 · 2021: 4 · 2020: 6 · 2019: 8 · 2018: 16 · 2017: 17 · 2016: 22 · 2015: 13 · 2014: 12 · 2013: 21 · 2012: 29
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- folic acid, colorectal cancer, colon cancer, one-carbon metabolism, folate deficiency, folic acid supplementation, chemoprevention, colorectal carcinogenesis, folate intake, oncogenic transformation, rodent models
- MeSH terms
- Colonic Neoplasms, Diet, Folic Acid, Health Promotion, Humans, Nutritional Physiological Phenomena, Anticarcinogenic Agents
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