Methylation of estrogen receptor alpha and mutL homolog 1 in normal colonic mucosa: association with folate and vitamin B-12 status in subjects with and without colorectal neoplasia

Reyad Al-Ghnaniem Abbadi, Jennifer Peters, Roberta Foresti, Nigel Heaton, Maria M Pufulete

Research output: Contribution to journalArticle (Academic Journal)

33 Citations (Scopus)

Abstract

BACKGROUND: Greater promoter methylation in some tumor-suppressor genes underlies most sporadic colorectal cancers and increases with age in the colon.

OBJECTIVE: We tested the hypothesis that biomarkers of folate and vitamin B-12 status are associated with estrogen receptor alpha (ERalpha) and mutL homolog 1 (MLH1) promoter methylation in subjects with and without neoplasia.

DESIGN: Biopsies of normal-appearing colorectal mucosa from 156 subjects with and without colorectal neoplasia (disease free, n = 76; cancer, n = 28; adenoma, n = 35; hyperplastic polyps, n = 17) were obtained at colonoscopy and used to evaluate methylation in 7 CpG sites in the ERalpha promoter and 13 CpG sites in the MLH1 promoter. Blood samples were obtained for the measurement of serum and red cell folate, serum vitamin B-12, and plasma homocysteine concentrations. Methylation indexes were generated to reflect an average methylation value across all CpG dinucleotides in both ERalpha and MLH1.

RESULTS: The methylation indexes for ERalpha and MLH1 generally were significantly (P < 0.05) higher in subjects with neoplasia than in disease-free subjects. The ERalpha methylation index correlated negatively with serum vitamin B-12 (r = -0.239, P = 0.003) and positively with plasma homocysteine (r = 0.188, P = 0.021). Disease status (P < 0.005), age (P < 0.001), and serum vitamin B-12 concentrations (P = 0.006) were independent determinants of ERalpha promoter methylation. Serum and red cell folate concentrations had no influence on ERalpha promoter methylation.

CONCLUSION: Serum vitamin B-12 but not folate status may be associated with ERalpha promoter methylation in normal-appearing colorectal mucosa.

Original languageEnglish
Pages (from-to)1064-1072
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Volume86
Issue number4
Publication statusPublished - Oct 2007

Keywords

  • Adaptor Proteins, Signal Transducing
  • Adenoma
  • Aged
  • Base Sequence
  • Biological Markers
  • Case-Control Studies
  • Colon
  • Colonic Polyps
  • Colorectal Neoplasms
  • DNA Methylation
  • Erythrocytes
  • Estrogen Receptor alpha
  • Female
  • Folic Acid
  • Homocysteine
  • Humans
  • Intestinal Mucosa
  • Male
  • Middle Aged
  • Nuclear Proteins
  • Nutritional Status
  • Vitamin B 12

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