title: Biomarkers related to one-carbon metabolism as potential risk factors for distal colorectal adenomas.
abstract: BACKGROUND
  Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no previous studies relating plasma concentrations of methionine, choline, and betaine to this outcome.
  
  
  METHODS
  This study comprised 10,601 individuals, 50 to 64 years of age, participating in the Norwegian Colorectal Cancer Prevention (NORCCAP) screening study. Using logistic regression analyses, we crosssectionally investigated associations between distal colorectal adenoma occurrence-potential precursor lesions of colorectal carcinomas-and plasma concentrations of methyl group donors and B-vitamins, and polymorphisms of genes related to one-carbon metabolism.
  
  
  RESULTS
  Screening revealed 1,809 subjects (17.1%) with at least one adenoma. The occurrence of high-risk adenomas (observed in 421 subjects) was inversely associated with plasma concentrations of methionine (highest versus lowest quartile: odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.45-0.83), betaine: OR = 0.74; 95% CI = 0.54-1.02, the vitamin B2 form flavin-mononucleotide (FMN): OR = 0.65; 95% CI = 0.49-0.88, and the vitamin B6 form pyridoxal 5'-phosphate (PLP): OR = 0.69; 95% CI = 0.51-0.95, but not with folate, choline, vitamin B12 concentrations, or with the studied polymorphisms. High methionine concentration in combination with high vitamin B2 or B6 concentrations was associated with lower occurrence of high-risk adenomas compared with these factors individually.
  
  
  CONCLUSIONS
  High plasma concentrations of methionine and betaine, and vitamins B2 and B6 may reduce risk of developing colorectal adenomas.
  
  
  CONCLUSIONS
  In addition to B-vitamins, methyl group donors such as methionine and betaine may play a role in colorectal carcinogenesis.
authors.affiliation: Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway. Stefan.Vogel@isf.uib.no
authors.forename: Stefan
authors.initials: S
authors.lastname: de Vogel
authors.forename: Jörn
authors.initials: J
authors.lastname: Schneede
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.forename: Ase
authors.initials: A
authors.lastname: Fredriksen
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.forename: Tone
authors.initials: T
authors.lastname: Bjørge
authors.forename: Ellen
authors.initials: E
authors.lastname: Kampman
authors.forename: Michael
authors.initials: M
authors.lastname: Bretthauer
authors.forename: Geir
authors.initials: G
authors.lastname: Hoff
mesh_terms: D000236:Adenoma / Q000097:blood* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D001622:Betaine / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000097:blood*; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D011110:Polymorphism, Genetic; D012256:Riboflavin / Q000097:blood*; D012307:Risk Factors; D025101:Vitamin B 6 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D001622:Betaine; D025101:Vitamin B 6; D008715:Methionine; D012256:Riboflavin