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Plasma Folate, Related Genetic Variants, and Colorectal Cancer Risk in EPIC

Eussen, Simone J. P. M.; Vollset, Stein Emil; Igland, Jannicke; Meyer, Klaus; Fredriksen, Ase; Ueland, Per Magne; Jenab, Mazda; Slimani, Nadia; Boffetta, Paolo and Overvad, Kim, et al. (2010) In Cancer Epidemiology Biomarkers & Prevention 19(5). p.1328-1340
Abstract
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; P-trend) for the fifth versus the first... (More)
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; P-trend) 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; P-trend) 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); <0.01]. Conclusions: This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms. Impact: Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions. Cancer Epidemiol Biomarkers Prev; 19(5); 1328-40. (C)2010 AACR. (Less)
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Cancer Epidemiology Biomarkers & Prevention
volume
19
issue
5
pages
1328 - 1340
publisher
American Association for Cancer Research
external identifiers
  • wos:000278489800021
  • scopus:77952019974
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-09-0841
language
English
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yes
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eb5674e3-d715-4f48-9d5a-3c88bb29807b (old id 1631521)
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2010-07-21 14:59:23
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@article{eb5674e3-d715-4f48-9d5a-3c88bb29807b,
  abstract     = {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; P-trend) for the fifth versus the first quintile of folate status was 0.94 (0.74-1.20; 0.44). The polymorphisms MTHFR677C -&gt; T, MTHFR1298A -&gt; C, MTR2756A -&gt; G, MTRR66A -&gt; G, and MTHFD11958G -&gt; 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; P-trend) 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 -&gt; A showed a positive association with CRC risk [RR AA versus GG 1.30 (1.06-1.59); &lt;0.01]. Conclusions: This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms. Impact: Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions. Cancer Epidemiol Biomarkers Prev; 19(5); 1328-40. (C)2010 AACR.},
  author       = {Eussen, Simone J. P. M. and Vollset, Stein Emil and Igland, Jannicke and Meyer, Klaus and Fredriksen, Ase and Ueland, Per Magne and Jenab, Mazda and Slimani, Nadia and Boffetta, Paolo and Overvad, Kim and Tjonneland, Anne and Olsen, Anja and Clavel-Chapelon, Francoise and Boutron-Ruault, Marie-Christine and Morois, Sophie and Weikert, Cornelia and Pischon, Tobias and Linseisen, Jakob and Kaaks, Rudolf and Trichopoulou, Antonia and Zilis, Demosthenes and Katsoulis, Michael and Palli, Domenico and Berrino, Franco and Vineis, Paolo and Tumino, Rosario and Panico, Salvatore and Peeters, Petra H. M. and Bueno-de-Mesquita, H. Bas and van Duijnhoven, Franzel J. B. and Gram, Inger Torhild and Skeie, Guri and Lund, Eiliv and Gonzalez, Carlos A. and Martinez, Carmen and Dorronsoro, Miren and Ardanaz, Eva and Navarro, Carmen and Rodriguez, Laudina and Van Guelpen, Bethany and Palmqvist, Richard and Manjer, Jonas and Ericson, Ulrika and Bingham, Sheila and Khaw, Kay-Tee and Norat, Teresa and Riboli, Elio},
  issn         = {1538-7755},
  language     = {eng},
  number       = {5},
  pages        = {1328--1340},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Plasma Folate, Related Genetic Variants, and Colorectal Cancer Risk in EPIC},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-09-0841},
  volume       = {19},
  year         = {2010},
}