title: Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk.
abstract: Despite extensive study, the role of folate in colorectal cancer remains unclear. Research has therefore begun to address the role of other elements of the folate-methionine metabolic cycles. This study investigated factors other than folate involved in one-carbon metabolism, i.e., choline, betaine, dimethylglycine, sarcosine, and methionine and relevant polymorphisms, in relation to the risk of colorectal cancer in a population with low intakes and circulating levels of folate.
  
  
  
  This was a prospective case-control study of 613 case subjects and 1,190 matched control subjects nested within the population-based Northern Sweden Health and Disease Study. We estimated odds ratios (OR) by conditional logistic regression, and marginal risk differences with weighted maximum likelihood estimation using incidence data from the study cohort.
  
  
  
  Higher plasma concentrations of methionine and betaine were associated with modest colorectal cancer risk reductions (OR [95% confidence interval {CI}] for highest versus lowest tertile: 0.76 [0.57, 0.99] and 0.72 [0.55, 0.94], respectively). Estimated marginal risk differences corresponded to approximately 200 fewer colorectal cancer cases per 100,000 individuals on average. We observed no clear associations between choline, dimethylglycine, or sarcosine and colorectal cancer risk. The inverse association of methionine was modified by plasma folate concentrations (OR [95% CI] for highest/lowest versus lowest/lowest tertile of plasma methionine/folate concentrations 0.39 [0.24, 0.64], Pinteraction = 0.06).
  
  
  
  In this population-based, nested case-control study with a long follow-up time from baseline to diagnosis (median: 8.2 years), higher plasma concentrations of methionine and betaine were associated with lower colorectal cancer risk.See Video Abstract at http://links.lww.com/EDE/B83.
authors.affiliation: From the aDepartment of Radiation Sciences, Oncology, bDepartment of Medical Biosciences, Pathology, cDepartment of Clinical Pharmacology, Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden; dDepartment of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway; eDepartment of Statistics, Umeå School of Business and Economics, fDepartment of Medical Biosciences, Clinical Chemistry, gDepartment of Biobank Research, Public Health and Clinical Medicine, and hDepartment of Odontology, Cariology, Umeå University, Umeå, Sweden.
authors.forename: Robin
authors.initials: R
authors.lastname: Myte
authors.forename: Björn
authors.initials: B
authors.lastname: Gylling
authors.forename: Jörn
authors.initials: J
authors.lastname: Schneede
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Jenny
authors.initials: J
authors.lastname: Häggström
authors.forename: Johan
authors.initials: J
authors.lastname: Hultdin
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Johansson
authors.forename: Richard
authors.initials: R
authors.lastname: Palmqvist
authors.forename: Bethany
authors.initials: B
authors.lastname: Van Guelpen
mesh_terms: D000368:Aged; D000596:Amino Acids / Q000097:blood*; D001622:Betaine / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D002794:Choline / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008715:Methionine / Q000097:blood; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D065840:Protective Factors; D012521:Sarcosine / Q000031:analogs & derivatives / Q000097:blood; D013548:Sweden / Q000453:epidemiology
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D014408:Biomarkers, Tumor; D001622:Betaine; C025138:dimethylglycine; D005492:Folic Acid; D008715:Methionine; D002794:Choline; D012521:Sarcosine