title: Methylation diet and methyl group genetics in risk for adenomatous polyp occurrence.
abstract: OBJECTIVE
  The aim of this study is to explore whether a methylation diet influences risk for adenomatous polyps (AP) either independently, or interactively with one-carbon metabolism-dependent gene variants, and whether such a diet modifies blood homocysteine, a biochemical phenotype closely related to the phenomenon of methylation.
  
  
  METHODS
  249 subjects were examined using selective fluorescence, PCR and food frequency questionnaire to determine homocysteine, nine methylation-related gene polymorphisms, dietary methionine, 5-methyltetrahydrofolate, vitamins B6 and B12.
  
  
  RESULTS
  1). Both dietary methionine and 5-methyltetrahydrofolate intake are significantly associated with plasma homocysteine. 2). Dietary methionine is related to AP risk in 2R3R-TS wildtype subjects, while dietary B12 is similarly related to this phenotype in individuals heterozygous for C1420T-SHMT, A2756G-MS and 844ins68-CBS, and in those recessive for 2R3R-TS. 3). Dietary methionine has a marginal influence on plasma homocysteine level in C1420T-SHMT heterozygotes, while B6 exhibits the same effect on homocysteine in C776G-TCN2 homozygote recessive subjects. Natural 5-methyltetrahydrofolate intake is interesting: Wildtype A1298C-MTHFR, heterozygote C677T-MTHFR, wildtype A2756G-MS and recessive A66G-MSR individuals all show a significant reciprocal association with homocysteine. 4). Stepwise regression of all genotypes to predict risk for AP indicated A2756G-MS and A66G-MSR to be most relevant (p = 0.0176 and 0.0408 respectively). Results were corrected for age and gender.
  
  
  CONCLUSIONS
  A methylation diet influences methyl group synthesis in the regulation of blood homocysteine level, and is modulated by genetic interactions. Methylation-related nutrients also interact with key genes to modify risk of AP, a precursor of colorectal cancer. Independent of diet, two methylation-related genes (A2756G-MS and A66G-MSR) were directly associated with AP occurrence.
authors.affiliation: School of Environmental & Life Sciences, University of Newcastle, PO Box 127, Brush Rd., Ourimbah, NSW 2258, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Lucock
authors.affiliation: Biomedical Sciences and Pharmacy, University of Newcastle, PO Box 127, Brush Rd., Ourimbah, NSW 2258, Australia.
authors.forename: Zoë
authors.initials: Z
authors.lastname: Yates
authors.affiliation: School of Environmental & Life Sciences, University of Newcastle, PO Box 127, Brush Rd., Ourimbah, NSW 2258, Australia.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Martin
authors.affiliation: School of Environmental & Life Sciences, University of Newcastle, PO Box 127, Brush Rd., Ourimbah, NSW 2258, Australia.
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Choi
authors.affiliation: School of Environmental & Life Sciences, University of Newcastle, PO Box 127, Brush Rd., Ourimbah, NSW 2258, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Beckett
authors.affiliation: School of Environmental & Life Sciences, University of Newcastle, PO Box 127, Brush Rd., Ourimbah, NSW 2258, Australia.
authors.forename: Lyndell
authors.initials: L
authors.lastname: Boyd
authors.affiliation: School of Environmental & Life Sciences, University of Newcastle, PO Box 127, Brush Rd., Ourimbah, NSW 2258, Australia.
authors.forename: Kathleen
authors.initials: K
authors.lastname: LeGras
authors.affiliation: School of Environmental & Life Sciences, University of Newcastle, PO Box 127, Brush Rd., Ourimbah, NSW 2258, Australia.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ng
authors.affiliation: Teaching & Research Unit, Central Coast Local Health District, PO Box 361, Gosford, NSW 2250, Australia.
authors.forename: Virginia
authors.initials: V
authors.lastname: Skinner
authors.affiliation: Teaching & Research Unit, Central Coast Local Health District, PO Box 361, Gosford, NSW 2250, Australia.
authors.forename: Ron
authors.initials: R
authors.lastname: Wai
authors.affiliation: School of Environmental & Life Sciences, University of Newcastle, PO Box 127, Brush Rd., Ourimbah, NSW 2258, Australia.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Kho
authors.affiliation: School of Environmental & Life Sciences, University of Newcastle, PO Box 127, Brush Rd., Ourimbah, NSW 2258, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Roach
authors.affiliation: Teaching & Research Unit, Central Coast Local Health District, PO Box 361, Gosford, NSW 2250, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Veysey
keywords: Adenomatous polyp; Colorectal cancer; Diet; Folate; Homocysteine; Methionine; Vitamin B12; Vitamin B6