TY - JOUR
TI - Plasma Folate, Related Genetic Variants, and Colorectal Cancer Risk in
EPIC
AU - Eussen, Simone J. P. M.
AU - Vollset, Stein Emil
AU - Igland, Jannicke and
AU - Meyer, Klaus
AU - Fredriksen, Ase
AU - Ueland, Per Magne
AU - Jenab, Mazda
AU - and Slimani, Nadia
AU - Boffetta, Paolo
AU - Overvad, Kim
AU - Tjonneland,
AU - Anne
AU - Olsen, Anja
AU - Clavel-Chapelon, Francoise
AU - Boutron-Ruault,
AU - Marie-Christine
AU - Morois, Sophie
AU - Weikert, Cornelia
AU - Pischon,
AU - Tobias
AU - Linseisen, Jakob
AU - Kaaks, Rudolf
AU - Trichopoulou, Antonia
AU - and Zilis, Demosthenes
AU - Katsoulis, Michael
AU - Palli, Domenico and
AU - Berrino, Franco
AU - Vineis, Paolo
AU - Tumino, Rosario
AU - Panico,
AU - Salvatore
AU - Peeters, Petra H. M.
AU - Bueno-de-Mesquita, H. Bas
AU - van
AU - Duijnhoven, Franzel J. B.
AU - Gram, Inger Torhild
AU - Skeie, Guri and
AU - Lund, Eiliv
AU - Gonzalez, Carlos A.
AU - Martinez, Carmen
AU - Dorronsoro,
AU - Miren
AU - Ardanaz, Eva
AU - Navarro, Carmen
AU - Rodriguez, Laudina and
AU - Van Guelpen, Bethany
AU - Palmqvist, Richard
AU - Manjer, Jonas and
AU - Ericson, Ulrika
AU - Bingham, Sheila
AU - Khaw, Kay-Tee
AU - Norat, Teresa
AU - and Riboli, Elio
JO - Cancer Epidemiology, Biomarkers & Prevention
PY - 2010
VL - 19
TODO - 5
SP - 1328-1340
PB - AMER ASSOC CANCER RESEARCH
SN - 1055-9965, 1538-7755
TODO - 10.1158/1055-9965.EPI-09-0841
TODO - null
TODO - 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. (C)2010
AACR.
ER -