Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition.
B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk.
Eussen
Simone J P M
SJ
LOCUS for homocysteine and related vitamins, Department of Pharmacology, Institute of Medicine, University of Bergen, and Haukeland University Hospital, Bergen, Norway. Simone.Eussen@farm.uib.no
Vollset
Stein Emil
SE
Hustad
Steinar
S
Midttun
Øivind
Ø
Meyer
Klaus
K
Fredriksen
Ase
A
Ueland
Per Magne
PM
Jenab
Mazda
M
Slimani
Nadia
N
Ferrari
Pietro
P
Agudo
Antonio
A
Sala
Núria
N
Capellá
Gabriel
G
Del Giudice
Giuseppe
G
Palli
Domenico
D
Boeing
Heiner
H
Weikert
Cornelia
C
Bueno-de-Mesquita
H Bas
HB
Büchner
Frederike L
FL
Carneiro
Fátima
F
Berrino
Franco
F
Vineis
Paolo
P
Tumino
Rosario
R
Panico
Salvatore
S
Berglund
Göran
G
Manjer
Jonas
J
Stenling
Roger
R
Hallmans
Göran
G
Martínez
Carmen
C
Arrizola
Larraitz
L
Barricarte
Aurelio
A
Navarro
Carmen
C
Rodriguez
Laudina
L
Bingham
Sheila
S
Linseisen
Jakob
J
Kaaks
Rudolf
R
Overvad
Kim
K
Tjønneland
Anne
A
Peeters
Petra H M
PH
Numans
Mattijs E
ME
Clavel-Chapelon
Françoise
F
Boutron-Ruault
Marie-Christine
MC
Morois
Sophie
S
Trichopoulou
Antonia
A
Lund
Eiliv
E
Plebani
Mario
M
Riboli
Elio
E
González
Carlos A
CA
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D019875:One-Carbon Group Transferases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012256:Riboflavin / Q000097:blood*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D025101:Vitamin B 6 / Q000097:blood*
D025101:Vitamin B 6; D019875:One-Carbon Group Transferases; D012256:Riboflavin