Cited by 386Folate and B Vitamins ResearchColorectal Cancer Treatments and StudiesNutritional Studies and Diet

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Role of Folate in Colon Cancer Development and Progression

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Kim, Young-In·2003·The Journal of Nutrition

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Abstract

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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Sorted by citations

Mendelian randomization
Sanderson, E., Glymour, M. M., Holmes, M. V., Kang, H., Morrison, J., Munafò, M. R., Palmer, T., Schooling, C. M., Wallace, C., Zhao, Q., et al. (2022) · Nature Reviews Methods Primers · doi:10.1038/s43586-021-00092-5 · Cited by 2,229
Is folic acid good for everyone?
Smith, A. D., Kim, Y., & Refsum, H. (2008) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.3.517 · Cited by 617
Self-citation
The role of folate receptor α in cancer development, progression and treatment: Cause, consequence or innocent bystander?
Kelemen, L. E. (2006) · International Journal of Cancer · doi:10.1002/ijc.21712 · Cited by 511
Folate and colorectal cancer: An evidence‐based critical review
Kim, Y. (2007) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200600191 · Cited by 422
Self-citation
A soybean cyst nematode resistance gene points to a new mechanism of plant resistance to pathogens
Liu, S., Kandoth, P. K., Warren, S., Yeckel, G., Heinz, R. D., Alden, J., Yang, C., Jamaï, A., El‐Mellouki, T., Juvale, P. S., et al. (2012) · Nature · doi:10.1038/nature11651 · Cited by 411

See all 386

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)
DOI: 10.1093/jn/133.11.3731s
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 7041 d)
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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Role of Folate in Colon Cancer Development and Progression

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