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The association of gastric cancer risk with plasma folate, cobalamin, and Methylenetetrahydrofolate reductase polymorphisms in the European prospective investigation into cancer and nutrition

Vollset, Stein Emil; Igland, Jannicke; Jenab, Mazda; Fredriksen, Ase; Meyer, Klaus; Eussen, Simone; Gjessing, Hakon K.; Ueland, Per Magne; Pera, Guillem and Sala, Nuria, et al. (2007) In Cancer Epidemiology Biomarkers & Prevention 16(11). p.2416-2424
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... (More)
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. (Less)
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Cancer Epidemiology Biomarkers & Prevention
volume
16
issue
11
pages
2416 - 2424
publisher
American Association for Cancer Research
external identifiers
  • wos:000251123500034
  • scopus:38849089220
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-07-0256
language
English
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yes
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61aaa68d-7fc5-4f41-b313-23cc6588fe4c (old id 969253)
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2008-01-30 09:52:21
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@article{61aaa68d-7fc5-4f41-b313-23cc6588fe4c,
  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.},
  author       = {Vollset, Stein Emil and Igland, Jannicke and Jenab, Mazda and Fredriksen, Ase and Meyer, Klaus and Eussen, Simone and Gjessing, Hakon K. and Ueland, Per Magne and Pera, Guillem and Sala, Nuria and Agudo, Antonio and Capella, Gabriel and Del Giudice, Giuseppe and Palli, Domenico and Boeing, Heiner and Weikert, Cornelia and Bueno-de-Mesquita, H. Bas and Carneiro, Fatima and Pala, Valeria and Vineis, Paolo and Tumino, Rosario and Panico, Salvatore and Berglund, Göran and Manjer, Jonas and Stenling, Roger and Hallmans, Goran and Martinez, Carmen and Dorronsoro, Miren and Barricarte, Aurelio and Navarro, Carmen and Quiros, Jose R. and Allen, Naomi and Key, Timothy J. and Bingham, Sheila and Linseisen, Jakob and Kaaks, Rudolf and Overvad, Kim and Tjonneland, Anne and Buchner, Frederike L. and Peeters, Petra H. M. and Numans, Mattijs E. and Clavel-Chapelon, Francoise and Boutron-Ruault, Marie-Christine and Trichopoulou, Antonia and Lund, Eiliv and Slimani, Nadia and Ferrari, Pietro and Riboli, Elio and Gonzalez, Carlos A.},
  issn         = {1538-7755},
  language     = {eng},
  number       = {11},
  pages        = {2416--2424},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {The association of gastric cancer risk with plasma folate, cobalamin, and Methylenetetrahydrofolate reductase polymorphisms in the European prospective investigation into cancer and nutrition},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-07-0256},
  volume       = {16},
  year         = {2007},
}