Plasma folate, related genetic variants, and colorectal cancer risk in EPIC.
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; 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].


CONCLUSIONS
This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms.


CONCLUSIONS
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.
Eussen
Simone J P M
SJ
LOCUS for homocysteine and related vitamins, Institute of Medicine, Section for Pharmacology, Department of Internal Medicine, University of Bergen, and Haukeland University Hospital, 5021 Laboratory Building, 9th floor, Bergen, Norway. Simone.Eussen@farm.uib.no
Vollset
Stein Emil
SE
Igland
Jannicke
J
Meyer
Klaus
K
Fredriksen
Ase
A
Ueland
Per Magne
PM
Jenab
Mazda
M
Slimani
Nadia
N
Boffetta
Paolo
P
Overvad
Kim
K
Tjønneland
Anne
A
Olsen
Anja
A
Clavel-Chapelon
Françoise
F
Boutron-Ruault
Marie-Christine
MC
Morois
Sophie
S
Weikert
Cornelia
C
Pischon
Tobias
T
Linseisen
Jakob
J
Kaaks
Rudolf
R
Trichopoulou
Antonia
A
Zilis
Demosthenes
D
Katsoulis
Michael
M
Palli
Domenico
D
Berrino
Franco
F
Vineis
Paolo
P
Tumino
Rosario
R
Panico
Salvatore
S
Peeters
Petra H M
PH
Bueno-de-Mesquita
H Bas
HB
van Duijnhoven
Fränzel J B
FJ
Gram
Inger Torhild
IT
Skeie
Guri
G
Lund
Eiliv
E
González
Carlos A
CA
Martínez
Carmen
C
Dorronsoro
Miren
M
Ardanaz
Eva
E
Navarro
Carmen
C
Rodríguez
Laudina
L
Van Guelpen
Bethany
B
Palmqvist
Richard
R
Manjer
Jonas
J
Ericson
Ulrika
U
Bingham
Sheila
S
Khaw
Kay-Tee
KT
Norat
Teresa
T
Riboli
Elio
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
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