Plasma folate, related genetic variants, and colorectal cancer risk in EPIC

Simone J P M Eussen, Stein Emil Vollset, Jannicke Igland, Klaus Meyer, Åse Fredriksen, Per Magne Ueland, Mazda Jenab, Nadia Slimani, Paolo Boffetta, Kim Overvad, Anne Tjønneland, Anja Olsen, Françoise Clavel-Chapelon, Marie Christine Boutron-Ruault, Sophie Morois, Cornelia Weikert, Tobias Pischon, Jakob Linseisen, Rudolf Kaaks, Antonia TrichopoulouDemosthenes Zilis, Michael Katsoulis, Domenico Palli, Franco Berrino, Paolo Vineis, Rosario Tumino, Salvatore Panico, Petra H M Peeters, H. Bas Bueno-de-Mesquita, Fränzel J B Van Duijnhoven, Inger Torhild Gram, Guri Skeie, Eiliv Lund, Carlos A. González, Carmen Martínez, Miren Dorronsoro, Eva Ardanaz, Carmen Navarro, Laudina Rodríguez, Bethany Van Guelpen, Richard Palmqvist, Jonas Manjer, Ulrika Ericson, Sheila Bingham, Kay Tee Khaw, Teresa Norat, Elio Riboli

Research output: Contribution to journalArticlepeer-review


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);

Original languageEnglish
Pages (from-to)1328-1340
Number of pages13
JournalCancer Epidemiology Biomarkers and Prevention
Issue number5
Publication statusPublished - May 2010

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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