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Does folic acid supplementation prevent or promote colorectal cancer? Results from model-based predictions.

Luebeck, E Georg and Moolgavkar, Suresh H and Liu, Amy Y and Boynton, Alanna and Ulrich, Cornelia M (2008) Does folic acid supplementation prevent or promote colorectal cancer? Results from model-based predictions. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 17 (6). pp. 1360-1367. ISSN 1055-9965

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Abstract

Folate is essential for nucleotide synthesis, DNA replication, and methyl group supply. Low-folate status has been associated with increased risks of several cancer types, suggesting a chemopreventive role of folate. However, recent findings on giving folic acid to patients with a history of colorectal polyps raise concerns about the efficacy and safety of folate supplementation and the long-term health effects of folate fortification. Results suggest that undetected precursor lesions may progress under folic acid supplementation, consistent with the role of folate role in nucleotide synthesis and cell proliferation. To better understand the possible trade-offs between the protective effects due to decreased mutation rates and possibly concomitant detrimental effects due to increased cell proliferation of folic acid, we used a biologically based mathematical model of colorectal carcinogenesis. We predict changes in cancer risk based on timing of treatment start and the potential effect of folic acid on cell proliferation and mutation rates. Changes in colorectal cancer risk in response to folic acid supplementation are likely a complex function of treatment start, duration, and effect on cell proliferation and mutations rates. Predicted colorectal cancer incidence rates under supplementation are mostly higher than rates without folic acid supplementation unless supplementation is initiated early in life (before age 20 years). To the extent to which this model predicts reality, it indicates that the effect on cancer risk when starting folic acid supplementation late in life is small, yet mostly detrimental. Experimental studies are needed to provide direct evidence for this dual role of folate in colorectal cancer and to validate and improve the model predictions.

Item Type: Article
Additional Information: This article is freely available via the URL above.
DOI: 10.1158/1055-9965.EPI-07-2878
PubMed ID: 18539928
NIHMSID: NIHMS121468
PMCID: PMC2834311
Grant Numbers: R01 CA105437-04, R01 CA059045-11, R01 CA107028-04
Keywords or MeSH Headings: Colorectal Neoplasms/chemically induced/metabolism/prevention & control; DNA Methylation/drug effects; DNA Replication/drug effects; Folic Acid/pharmacology; Humans; Models, Statistical; Mutation; Risk;
Subjects: Diseases > Solid tumors > Digestive system cancer
Research Methodologies > Computational Biology > Modeling
Research Methodologies > Epidemiology > Risk assessment
Therapeutics > Drug Therapy
Depositing User: Library Staff
Date Deposited: 02 Jun 2009 20:44
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/296

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