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

Oleh:

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

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The American Journal of Clinical Nutrition vol. 86 no. 04 (Oct. 2007), page 1064.
Topik: Folate ; vitamin B-12 ; homocysteine ; • DNA methylation ; estrogen receptor ; ER ; mutL homolog 1 ; MLH1 ; colorectal cancer ; colorectal adenoma ; hyperplastic polyps

Ketersediaan

Perpustakaan FK Nomor Panggil: A07.K.2007.04 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

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

Opini Anda

Klik untuk menuliskan opini Anda tentang koleksi ini!

Kembali