title: The association of gastric cancer risk with plasma folate, cobalamin, and methylenetetrahydrofolate reductase polymorphisms in the European Prospective Investigation into Cancer and Nutrition.
abstract: Previous studies have shown inconsistent associations of folate intake and polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene with gastric cancer risk. Our nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort is the first prospective study of blood folate levels and gastric cancer. Gastric cancer cases (n=247) and controls (n=631) were matched for study center, age, sex, and time of blood donation. Two common single nucleotide polymorphisms of the MTHFR gene were determined, as were plasma concentrations of folate, cobalamin (vitamin B12), total homocysteine, and methylmalonic acid (cobalamin deficiency marker) in prediagnostic plasma. Risk measures were calculated with conditional logistic regression. Although no relations were observed between plasma folate or total homocysteine concentrations and gastric cancer, we observed a trend toward lower risk of gastric cancer with increasing cobalamin concentrations (odds ratio, 0.79 per SD increase in cobalamin; P=0.01). Further analyses showed that the inverse association between cobalamin and gastric cancer was confined to cancer cases with low pepsinogen A levels (marker of severe chronic atrophic gastritis) at the time of blood sampling. The 677 C-->T MTHFR polymorphism was not associated with gastric cancer, but we observed an increased risk with the variant genotype of the 1298 A-->C polymorphism (odds ratio, 1.47 for CC versus AA; P=0.04). In conclusion, we found no evidence of a role of folate in gastric cancer etiology. However, we observed increased gastric cancer risk at low cobalamin levels that was most likely due to compromised cobalamin status in atrophic gastritis preceding gastric cancer.
authors.affiliation: LOCUS for Homocysteine and Related Vitamins, Institute of Medicine, University of Bergen, Bergen, Norway. vollset@uib.no
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.forename: Jannicke
authors.initials: J
authors.lastname: Igland
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: Ase
authors.initials: A
authors.lastname: Fredriksen
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.forename: Simone
authors.initials: S
authors.lastname: Eussen
authors.forename: Håkon K
authors.initials: HK
authors.lastname: Gjessing
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Guillem
authors.initials: G
authors.lastname: Pera
authors.forename: Núria
authors.initials: N
authors.lastname: Sala
authors.forename: Antonio
authors.initials: A
authors.lastname: Agudo
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.forename: Valeria
authors.initials: V
authors.lastname: Pala
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: Göran
authors.initials: G
authors.lastname: Berglund
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.forename: Roger
authors.initials: R
authors.lastname: Stenling
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: José R
authors.initials: JR
authors.lastname: Quirós
authors.forename: Naomi
authors.initials: N
authors.lastname: Allen
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.forename: Sheila
authors.initials: S
authors.lastname: Bingham
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Frederike L
authors.initials: FL
authors.lastname: Büchner
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Mattijs E
authors.initials: ME
authors.lastname: Numans
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Nadia
authors.initials: N
authors.lastname: Slimani
authors.forename: Pietro
authors.initials: P
authors.lastname: Ferrari
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Carlos A
authors.initials: CA
authors.lastname: González
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005757:Gastritis, Atrophic / Q000097:blood / Q000453:epidemiology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics*; D008764:Methylmalonic Acid / Q000097:blood; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12