Plasma methionine,choline, betaine,and dimethylglycine in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) |
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| Affiliation: | 1. Departments of Global Public Health and Primary Care;2. Clinical Science, Section for Pharmacology, University of Bergen, Bergen, Norway;3. Department of Epidemiology, School for Public Health and Primary Care, CAPHRI, Maastricht University, Maastricht, The Netherlands;4. BEVITAL AS, Bergen;5. Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen;6. Departments of Clinical Science, Section of Cardiology, University of Bergen, Bergen;7. Heart Disease, Haukeland University Hospital, Bergen;8. Norwegian Institute of Public Health, Bergen, Norway;9. Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark;10. INSERM, Centre for Research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women''s Health Team, Villejuif;11. Paris South University, Villejuif;12. IGR, Villejuif;13. INSERM, Research Centre ‘Lipids, Nutrition, Cancer’, Dijon, Franc;14. German Cancer Research Center (DKFZ), Heidelberg, Germany;15. Hellenic Health Foundation, Athens;16. WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece;17. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano;18. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, Florence;19. Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples;20. Cancer Registry and Histopathology Unit, ‘Civile - M.P. Arezzo’ Hospital, ASP, Ragusa;21. School of Public Health and HuGeF Foundation, Torino, Italy;22. The School of Public Health, Imperial College London, London, UK;23. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands;24. Department of Gastroenterology and Hepatology;25. Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands;26. Department of Community Medicine, Faculty of Health Sciences, UIT The Arctic University of Norway, Tromsø;27. Department of Research, Cancer Registry of Norway, Oslo, Norway;28. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;29. Department of Genetic Epidemiology, Samfundet Folkhälsan, Helsinki, Finland;30. Basque Regional Health Department, Public Health Direction and Biodonostia Research Institute (CIBERESP), San Sebastian;31. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Barcelona;32. Andalusian School of Public Health, Granada;33. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid;34. Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada;35. Public Health Directorate, Asturias, Oviedo;36. Department of Epidemiology, Regional Health Council, Murcia;37. Public Health Institute of Navarra, Pamplona;38. Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Spain;39. Department of Biobank Research, Umeå University, Umeå, Sweden;40. International Agency for Research on Cancer (IARC-WHO), Lyon, France;41. Department of Radiation Sciences, Oncology, University of Umeå, Umeå, Sweden;42. University of Cambridge School of Clinical Medicine, Cambridge;43. MRC Epidemiology Unit, University of Cambridge, Cambridge, UK |
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| Abstract: | BackgroundDisturbances in one carbon metabolism may contribute to carcinogenesis by affecting methylation and synthesis of DNA. Choline and its oxidation product betaine are involved in this metabolism and can serve as alternative methyl group donors when folate status is low.Patients and methodsWe conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), to investigate plasma concentrations of the methyl donors methionine, choline, betaine (trimethylglycine), and dimethylglycine (DMG) in relation to colorectal cancer (CRC) risk. Our study included 1367 incident CRC cases (965 colon and 402 rectum) and 2323 controls matched by gender, age group, and study center. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for CRC risk were estimated by conditional logistic regression, comparing the fifth to the first quintile of plasma concentrations.ResultsOverall, methionine (OR: 0.79, 95% CI: 0.63–0.99, P-trend = 0.05), choline (OR: 0.77, 95% CI: 0.60–0.99, P-trend = 0.07), and betaine (OR: 0.85, 95% CI: 0.66–1.09, P-trend = 0.06) concentrations were inversely associated with CRC risk of borderline significance. In participants with folate concentration below the median of 11.3 nmol/l, high betaine concentration was associated with reduced CRC risk (OR: 0.71, 95% CI: 0.50–1.00, P-trend = 0.02), which was not observed for those having a higher folate status. Among women, but not men, high choline concentration was associated with decreased CRC risk (OR: 0.62, 95% CI: 0.43–0.88, P-trend = 0.01). Plasma DMG was not associated with CRC risk.ConclusionsIndividuals with high plasma concentrations of methionine, choline, and betaine may be at reduced risk of CRC. |
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