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Unmetabolized Folic Acid in Prediagnostic Plasma and the Risk of Colorectal Cancer.

ABSTRACT: Higher folate has been associated with a reduced colorectal cancer (CRC) risk, but excessive folate may promote tumor progression. The role of unmetabolized folic acid (UFA) from high folic acid consumption in carcinogenesis is largely unexplored. We evaluated prediagnostic plasma levels of UFA in relation to CRC risk in nested case-control studies (618 CRC case patients and 1207 matched control) with blood samples collected prior to folic acid fortification. UFA was detected in 21.4% of control UFA levels were not associated with CRC risk. Compared with undetectable levels, the multivariable relative risks (RRs) of CRC were 1.03 (95% confidence interval [CI] = 0.73 to 1.46) for less than 0.5 nmol/L and 1.12 (95% CI = 0.81 to 1.55) for 0.5 nmol/L or more (Ptrend = .32). A positive association between UFA levels and CRC risk was observed among men (RR = 1.57, 95% CI = 0.99 to 2.49 for ?0.5 nmol/L vs undetectable, Pinteraction = .04), and a positive association was also observed among those with the methylene-tetrahydrofolate reductase (MTHFR) CT/TT genotype (RR = 2.20, 95% CI = 1.22 to 3.94 for ?0.5 nmol/L vs undetectable, Pinteraction=0.02). In conclusion, prediagnostic plasma levels of UFA from the prefortification period were not associated with risk of CRC.

SUBMITTER: Cho E

PROVIDER: S-EPMC4715248 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Unmetabolized Folic Acid in Prediagnostic Plasma and the Risk of Colorectal Cancer.

Cho Eunyoung E Zhang Xuehong X Townsend Mary K MK Selhub Jacob J Paul Ligi L Rosner Bernard B Fuchs Charles S CS Willett Walter C WC Giovannucci Edward L EL

Journal of the National Cancer Institute 20150915 12

Higher folate has been associated with a reduced colorectal cancer (CRC) risk, but excessive folate may promote tumor progression. The role of unmetabolized folic acid (UFA) from high folic acid consumption in carcinogenesis is largely unexplored. We evaluated prediagnostic plasma levels of UFA in relation to CRC risk in nested case-control studies (618 CRC case patients and 1207 matched control) with blood samples collected prior to folic acid fortification. UFA was detected in 21.4% of control ...[more]

PMID: 26376686

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Project description:BackgroundThere is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized clinical trial has been conducted to examine the FA-UMFA dose-response relationship.ObjectiveThis study aimed to investigate the FA-UMFA dose-response relationship in Chinese adults with hypertension and elevated homocysteine (H-type hypertension), a population with clear clinical indication for FA treatment.MethodsThe data for this study were derived from a randomized, double-blind, multicenter clinical trial of 8 FA dosages on efficacy of homocysteine (Hcy) lowering. The parent trial had three 3 stages: screening period (2-10 days), run-in period (0-2 weeks, baseline visit), and double-blind treatment period (8 weeks) with follow-up visits at the end of the 2nd, 4th, 6th, and 8th weeks of treatment. Participants were randomly assigned to 8 treatment groups corresponding to FA dosages of 0, 0.4, 0.6, 0.8, 1.2, 1.6, 2.0 mg to 2.4 mg.ResultsThis study included 1,567 Chinese adults aged ≥45 years with H-type hypertension. There was a positive but non-linear association between FA supplementation and UMFA levels in the dosage range of 0 mg to 2.4 mg. In the regression analysis, the coefficients for the linear and quadratic terms of FA dosage were both statistically significant (P < 0.001). Notably, the slope for UMFA was greater for FA dosages >0.8 mg (ß = 11.21, 95% CI: 8.97, 13.45) compared to FA dosages ≤0.8 mg (ß = 2.94, 95% CI: 2.59, 3.29). Furthermore, FA dosages higher than 0.8 mg did not confer additional benefits in terms of increasing 5-methyl tetrahydrofolic acid (5-MTHF, active form of folate) or reducing homocysteine (Hcy).ConclusionIn Chinese adults with H-type hypertension, this study showed a positive, non-linear, dosage-response relationship between FA supplementation ranging from 0 to 2.4 mg and circulating UMFA levels. It revealed that 0.8 mg FA is an optimal dosage in terms of balancing efficacy (increasing 5-MTHF and lowering Hcy) while minimizing undesirable elevation of UMFA.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03472508?term=NCT03472508&draw=2&rank=1, identifier NCT03472508.

Dataset Information

Unmetabolized Folic Acid in Prediagnostic Plasma and the Risk of Colorectal Cancer.

Publications

Unmetabolized Folic Acid in Prediagnostic Plasma and the Risk of Colorectal Cancer.

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