TY - JOUR
T1 - The association of gastric cancer risk with plasma folate, cobalamin, and Methylenetetrahydrofolate reductase polymorphisms in the European prospective investigation into cancer and nutrition
AU - Vollset, Stein Emil
AU - Igland, Jannicke
AU - Jenab, Mazda
AU - Fredriksen, Åse
AU - Meyer, Klaus
AU - Eussen, Simone
AU - Gjessing, Håkon K.
AU - Ueland, Per Magne
AU - Pera, Guillem
AU - Sala, Núria
AU - Agudo, Antonio
AU - Capella, Gabriel
AU - Del Giudice, Giuseppe
AU - Palli, Domenico
AU - Boeing, Heiner
AU - Weikert, Cornelia
AU - Bueno-De-Mesquita, H. Bas
AU - Carneiro, Fátima
AU - Pala, Valeria
AU - Vineis, Paolo
AU - Tumino, Rosario
AU - Panico, Salvatore
AU - Berglund, Göran
AU - Manjer, Jonas
AU - Stenling, Roger
AU - Hallmans, Göran
AU - Martínez, Carmen
AU - Dorronsoro, Miren
AU - Barricarte, Aurelio
AU - Navarro, Carmen
AU - Quirós, José R.
AU - Allen, Naomi
AU - Key, Timothy J.
AU - Bingham, Sheila
AU - Linseisen, Jakob
AU - Kaaks, Rudolf
AU - Overvad, Kim
AU - Tjøneland, Anne
AU - Büchner, Frederike L.
AU - Peeters, Petra H M
AU - Numans, Mattijs E.
AU - Clavel-Chapelon, Françoise
AU - Boutron-Ruault, Marie Christine
AU - Trichopoulou, Antonia
AU - Lund, Eiliv
AU - Slimani, Nadia
AU - Ferrari, Pietro
AU - Riboli, Elio
AU - González, Carlos A.
PY - 2007/11/1
Y1 - 2007/11/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1055-9965.EPI-07-0256
DO - 10.1158/1055-9965.EPI-07-0256
M3 - Article
C2 - 18006931
AN - SCOPUS:38849089220
VL - 16
SP - 2416
EP - 2424
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 11
ER -