title: 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; 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.
authors.affiliation: 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
authors.forename: Simone J P M
authors.initials: SJ
authors.lastname: Eussen
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.forename: Jannicke
authors.initials: J
authors.lastname: Igland
authors.forename: Klaus
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authors.lastname: Meyer
authors.forename: Ase
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authors.lastname: Ueland
authors.forename: Mazda
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authors.lastname: Jenab
authors.forename: Nadia
authors.initials: N
authors.lastname: Slimani
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Sophie
authors.initials: S
authors.lastname: Morois
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
authors.forename: Tobias
authors.initials: T
authors.lastname: Pischon
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Zilis
authors.forename: Michael
authors.initials: M
authors.lastname: Katsoulis
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Franco
authors.initials: F
authors.lastname: Berrino
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Fränzel J B
authors.initials: FJ
authors.lastname: van Duijnhoven
authors.forename: Inger Torhild
authors.initials: IT
authors.lastname: Gram
authors.forename: Guri
authors.initials: G
authors.lastname: Skeie
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Carlos A
authors.initials: CA
authors.lastname: González
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Laudina
authors.initials: L
authors.lastname: Rodríguez
authors.forename: Bethany
authors.initials: B
authors.lastname: Van Guelpen
authors.forename: Richard
authors.initials: R
authors.lastname: Palmqvist
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.forename: Ulrika
authors.initials: U
authors.lastname: Ericson
authors.forename: Sheila
authors.initials: S
authors.lastname: Bingham
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Teresa
authors.initials: T
authors.lastname: Norat
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
mesh_terms: 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
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
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