title: Low folate levels are associated with reduced risk of colorectal cancer in a population with low folate status.
abstract: BACKGROUND
  A diet rich in folate is associated with a reduced colorectal cancer risk, whereas the role of circulating levels is less clear. The aim of this study was to relate prediagnostic plasma folate, vitamin B12, and homocysteine concentrations to the risk of colorectal cancer.
  
  
  METHODS
  This was a prospective case-control study of 331 cases and 662 matched controls nested within the population-based Northern Sweden Health and Disease Study. Median follow-up time from recruitment to diagnosis was 10.8 years.
  
  
  RESULTS
  Plasma folate concentrations were positively related to colorectal cancer risk; multivariate odds ratios were 1.62 [95% confidence intervals (CI), 1.08-2.42] and 1.42 (95% CI, 0.94-2.21) for the middle and highest versus lowest tertile, respectively. In subjects with follow-up <10.8 years, a statistically significant doubled risk was observed for the middle and highest versus lowest tertile, whereas findings for longer follow-up times were null. A positive risk relationship was also observed for tumor stage III-IV but not I-II. Plasma vitamin B12 concentrations were inversely associated with rectal cancer risk. Homocysteine was not significantly related to colorectal cancer risk.
  
  
  CONCLUSIONS
  In this population-based, nested case-control study, low plasma folate concentrations were associated with a reduced colorectal cancer risk. This protective role was mainly observed in subjects with higher tumor stage or shorter follow-up time between recruitment and diagnosis. Low circulating folate status may protect against colorectal cancer or suppress progression of preneoplastic or neoplastic lesions.
  
  
  CONCLUSIONS
  These findings may have relevance for the ongoing debate about mandatory folic acid fortification of flour.
authors: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors: Björn
authors: B
authors: Gylling
authors: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors: Bethany
authors: B
authors: Van Guelpen
authors: Department of Clinical Pharmacology, Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden.
authors: Jörn
authors: J
authors: Schneede
authors: Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
authors: Johan
authors: J
authors: Hultdin
authors: Department of Clinical Science, Pharmacology, University of Bergen, Bergen, Norway.
authors: Per Magne
authors: PM
authors: Ueland
authors: Department of Biobank Research, Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors: Göran
authors: G
authors: Hallmans
authors: Department of Odontology, Cariology, Umeå University, Umeå, Sweden.
authors: Ingegerd
authors: I
authors: Johansson
authors: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. Richard.Palmqvist@medbio.umu.se.
authors: Richard
authors: R
authors: Palmqvist
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D015179:Colorectal Neoplasms / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D053719:Tandem Mass Spectrometry
chemical_list: D005492:Folic Acid