title: Short-term folate supplementation in physiological doses has no effect on ESR1 and MLH1 methylation in colonic mucosa of individuals with adenoma.
abstract: OBJECTIVE
  Low folate intake may increase risk of colorectal cancer by altering gene-specific methylation in the colon. We determined whether supplementation with physiological doses of folate could alter methylation in the oestrogen receptor 1 (ESR1) and mutL homolog 1 (MLH1) genes in colonic mucosa of subjects with colorectal adenoma.
  
  
  METHODS
  This was a randomised, double-blind, placebo-controlled trial. Subjects received either 400 µg/day folic acid (n = 15) or placebo (n = 14) for 10 weeks. Blood and colonic tissue samples were collected at baseline and after intervention to determine biomarkers of folate and vitamin B12 status, MTHFR C677T and MS A2756G genotypes, and ESR1 and MLH1 methylation.
  
  
  RESULTS
  Although serum and red cell folate increased (p < 0.001 vs. placebo) and plasma homocysteine decreased (p = 0018 vs. placebo) in the folic acid group, there were no significant changes in ESR1 (p = 0.649 vs. placebo) or MLH1 (p = 0.211 vs. placebo) methylation. There was a significant effect of gender on ESR1 methylation (p = 0.004) and significant gender and genotype (MTHFR C677T and MS A2756G) interactions (p = 0.04 and p = 0.014, respectively) that were independent of treatment group allocation.
  
  
  CONCLUSIONS
  Short-term folate supplementation in physiological doses decreases plasma homocysteine but has no effect on ESR1 and MLH1 methylation in colonic mucosa of individuals with adenoma. Further studies to investigate the interactions between gender, genotype and DNA methylation suggested in this study are warranted.
authors: Diabetes and Nutritional Sciences Division, King's College London, London, UK.
authors: Reyad
authors: R
authors: Al-Ghnaniem Abbadi
authors: Peter
authors: P
authors: Emery
authors: Maria
authors: M
authors: Pufulete
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000236:Adenoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010919:Placebos; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D010919:Placebos; D005492:Folic Acid; D000070957:MutL Protein Homolog 1