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 α (ERα) 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 ERα 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 ERα and MLH1.Results: The methylation indexes for ERα and MLH1 generally were significantly (P < 0.05) higher in subjects with neoplasia than in disease-free subjects. The ERα 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 ERα promoter methylation. Serum and red cell folate concentrations had no influence on ERα promoter methylation.Conclusion: Serum vitamin B-12 but not folate status may be associated with ERα promoter methylation in normal-appearing colorectal mucosa.
Published Version
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