title: B vitamins, methionine and alcohol intake and risk of colon cancer in relation to BRAF mutation and CpG island methylator phenotype (CIMP).
abstract: BACKGROUND
  One-carbon metabolism appears to play an important role in DNA methylation reaction. Evidence suggests that a low intake of B vitamins or high alcohol consumption increases colorectal cancer risk. How one-carbon nutrients affect the CpG island methylator phenotype (CIMP) or BRAF mutation status in colon cancer remains uncertain.
  
  
  METHODS
  Utilizing incident colon cancers in a large prospective cohort of women (the Nurses' Health Study), we determined BRAF status (N = 386) and CIMP status (N = 375) by 8 CIMP-specific markers [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1], and 8 other CpG islands (CHFR, HIC1, IGFBP3, MGMT, MINT-1, MINT-31, p14, and WRN). We examined the relationship between intake of one-carbon nutrients and alcohol and colon cancer risk, by BRAF mutation or CIMP status.
  
  
  RESULTS
  Higher folate intake was associated with a trend towards low risk of CIMP-low/0 tumors [total folate intake ≥400 µg/day vs. <200 µg/day; the multivariate relative risk = 0.73; 95% CI = 0.53-1.02], whereas total folate intake had no influence on CIMP-high tumor risks (P(heterogeneity) = 0.73). Neither vitamin B(6), methionine or alcohol intake appeared to differentially influence risks for CIMP-high and CIMP-low/0 tumors. Using the 16-marker CIMP panel did not substantially alter our results. B vitamins, methionine or alcohol intake did not affect colon cancer risk differentially by BRAF status.
  
  
  CONCLUSIONS
  This molecular pathological epidemiology study suggests that low level intake of folate may be associated with an increased risk of CIMP-low/0 colon tumors, but not that of CIMP-high tumors. However, the difference between CIMP-high and CIMP-low/0 cancer risks was not statistically significant, and additional studies are necessary to confirm these observations.
authors: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. eva.schernhammer@channing.harvard.edu
authors: Eva S
authors: ES
authors: Schernhammer
authors: Edward
authors: E
authors: Giovannucci
authors: Yoshifumi
authors: Y
authors: Baba
authors: Charles S
authors: CS
authors: Fuchs
authors: Shuji
authors: S
authors: Ogino
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D020747:Calcium Channels, T-Type / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D003110:Colonic Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008715:Methionine / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012307:Risk Factors; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics; D011795:Surveys and Questionnaires; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D020747:Calcium Channels, T-Type; D018797:Cell Cycle Proteins; D050677:Core Binding Factor Alpha 3 Subunit; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005492:Folic Acid; D007335:Insulin-Like Growth Factor II; D051741:Kruppel-Like Transcription Factors; D008715:Methionine; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D048493:Proto-Oncogene Proteins B-raf; D018168:Receptors, Retinoic Acid; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D044767:Ubiquitin-Protein Ligases; C121855:CACNA1G protein, human; C499808:HIC1 protein, human; C035170:IGF2 protein, human; C501486:MLH1 protein, human; C105389:NEUROG1 protein, human; C493729:Runx3 protein, human; C108944:SOCS1 protein, human; C082927:retinoic acid binding protein I, cellular; C412002:CHFR protein, human; C482119:BRAF protein, human