The EPIC-Norfolk Study
Plasma folate, related genetic variants, and colorectal cancer risk in EPIC.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2010 ; 19: 1328-40.
Eussen SJ, Vollset SE, Igland J, Meyer K, Fredriksen A, Ueland PM, Jenab M, Slimani N, Boffetta P, Overvad K, Tjønneland A, Olsen A, Clavel-Chapelon F, Boutron-Ruault MC, Morois S, Weikert C, Pischon T, Linseisen J, Kaaks R, Trichopoulou A, Zilis D, Katsoulis M, Palli D, Berrino F, Vineis P, Tumino R, Panico S, Peeters PH, Bueno-de-Mesquita HB, van Duijnhoven FJ, Gram IT, Skeie G, Lund E, González CA, Martínez C, Dorronsoro M, Ardanaz E, Navarro C, Rodriguez L, Van Guelpen B, Palmqvist R, Manjer J, Ericson U, Bingham S, Khaw KT, Norat T, and Riboli E
DOI : 10.1158/1055-9965.EPI-09-0841
PubMed ID : 20447924
PMCID : PMC2880712
URL : https://cebp.aacrjournals.org/lookup/doi/10.1158/1055-9965.EPI-09-0841
Abstract
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.
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.
Overall analyses did not reveal associations of plasma folate with CRC. The RR (95% confidence interval; Ptrend) 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; Ptrend) 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].
This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms.
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.