Plasma Folate, Related Genetic Variants, and Colorectal Cancer Risk in EPIC

Abstract

Background: A potential dual role of folate in colorectal cancer (CRC) is currently subject to debate. We investigate the associations between plasma folate, several relevant folate-related polymorphisms, and CRC risk within the large European Prospective Investigation into Cancer and Nutrition cohort.Methods: In this nested case-control study, 1,367 incident CRC cases were matched to 2,325 controls for study center, age, and sex. Risk ratios (RR) were estimated with conditional logistic regression and adjusted for smoking, education, physical activity, and intake of alcohol and fiber.Results: Overall analyses did not reveal associations of plasma folate with CRC. The RR (95% confidence interval; P trend ) for the fifth versus the first quintile of folate status was 0.94 (0.74-1.20; 0.44). The polymorphisms MTHFR677C→T, MTHFR1298A→C, MTR2756A→G, MTRR66A→G, and MTHFD11958G→A were not associated with CRC risk. However, in individuals with the lowest plasma folate concentrations, the MTHFR 677TT genotype showed a statistically nonsignificant increased CRC risk [RR (95% CI; P trend ) TT versus CC = 1.39 (0.87-2.21); 0.12], whereas those with the highest folate concentrations showed a nonsignificant decreased CRC risk [RR TT versus CC = 0.74 (0.39-1.37); 0.34]. The SLC19A180G→A showed a positive association with CRC risk [RR AA versus GG 1.30 (1.06-1.59); <0.01].Conclusions: This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms.Impact: Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions. Cancer Epidemiol Biomarkers Prev; 19(5); 1328-40. ©2010 AACR.

Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas

“…There was a weak inverse association between dietary folate intake and colorectal cancer risk (14), and blood folate levels were inversely associated in some (15)(16)(17)(18), but not all (10,(19)(20)(21)(22)(23)(24) studies. Vitamin B12 status was not associated with colorectal cancer in the majority of the studies (21,(24)(25)(26).…”

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“…The equivalent of 60 minutes of exercise per day to be physically active; consume a plant-based diet comprising a variety of fruits and vegetables; choose unprocessed cereals and grains over processed products; limit the intake of red meat and salt; avoid or limit alcohol consumption, to meet nutritional needs without the use of food supplements [218] avoid energy-rich foods, sugary drinks, fast foods and processed meat, and genetically modified foods modified to increase certain types of cancer (such as colorectal cancer) by modification in the nucleic acids thus causing changes in enzymatic activity [219,220,223,224].…”

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