Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer.
DNA hypomethylation may increase the risk of colorectal cancer. The main aim of this study was to assess the influence of folate status (serum and erythrocyte folate and plasma homocysteine concentrations) on DNA methylation. Methylenetetrahydrofolate reductase (MTHFR 677C --> T and 1298A --> C), methionine synthase (MS 2756A --> G) and cystathionine synthase (CBS 844ins68) polymorphisms were measured to account for potential confounding effects on folate status and DNA methylation. A total of 68 subjects (33 men and 35 women, 36-78 years) free from colorectal polyps or cancer were recruited in a cross-sectional study. Tissue biopsies were obtained at colonoscopy for the determination of DNA methylation in colonic mucosa using an in vitro radiolabelled methyl acceptance assay. Serum and erythrocyte folate were inversely correlated with plasma homocysteine (r=-0.573, P<0.001 and r=-0.307, P=0.01 respectively) and DNA hypomethylation in colonic mucosa (r=-0.311, P=0.01 and r=-0.356, P=0.03). After adjusting for gender, age, body mass index, smoking and genotype, there were weak negative associations between serum and erythrocyte folate and colonic DNA hypomethylation (P=0.07 and P=0.08, respectively).
Pufulete
M
M
Nutritional Sciences Research Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. maria.pufulete@kcl.ac.uk
Al-Ghnaniem
R
R
Rennie
J A
JA
Appleby
P
P
Harris
N
N
Gout
S
S
Emery
P W
PW
Sanders
T A
TA
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000428:Alcohol Drinking; D003106:Colon / Q000166:cytology* / Q000201:enzymology; D003113:Colonoscopy; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000201:enzymology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
D006710:Homocysteine; D004247:DNA; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D003541:Cystathionine beta-Synthase
Hum Mol Genet. 1996 Dec;5(12):1867-74
8968737
Int J Cancer. 1997 Mar 17;70(6):644-8
9096643
Atherosclerosis. 1998 Feb;136(2):347-54
9543106
Am J Hum Genet. 1998 May;62(5):1044-51
9545395
Ann Intern Med. 1998 Oct 1;129(7):517-24
9758570
Br J Cancer. 1999 Apr;79(11-12):1917-22
10206314
Mol Genet Metab. 1999 Aug;67(4):352-6
10444346
Cancer Epidemiol Biomarkers Prev. 1999 Sep;8(9):825-9
10498402
Genet Epidemiol. 1999 Nov;17(4):298-309
10520212
Cancer Epidemiol Biomarkers Prev. 2000 Jul;9(7):657-63
10919734
Cancer Epidemiol Biomarkers Prev. 2000 Aug;9(8):849-53
10952104
Atherosclerosis. 2001 Feb 15;154(3):667-72
11257268
Am J Med Genet. 2001 Jul 1;101(3):246-54
11424140
Cancer Res. 2001 Oct 1;61(19):6991-5
11585722
Int J Cancer. 2002 Feb 20;97(6):864-7
11857369
Gut. 2002 Apr;50(4):520-4
11889073
Am J Obstet Gynecol. 2002 Mar;186(3):499-503
11904614
Br J Nutr. 2002 Apr;87(4):383-90
12064348
Anal Chem. 2002 Sep 1;74(17):4526-31
12236365
Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1611-21
12496052
Gastroenterology. 2003 May;124(5):1240-8
12730865
Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):5860-5
14676107
Anticancer Res. 2004 Mar-Apr;24(2B):649-54
15161007
Cancer Causes Control. 2004 Jun;15(5):493-501
15286469
J Nutr Biochem. 2004 Sep;15(9):554-60
15350988
Nature. 1983 Jan 6;301(5895):89-92
6185846
Science. 1985 Apr 12;228(4696):187-90
2579435
Int J Cancer. 1991 Sep 9;49(2):161-7
1652565
Br J Cancer. 1992 May;65(5):667-72
1586594
J Natl Cancer Inst. 1993 Jun 2;85(11):875-84
8492316
Biochem Biophys Res Commun. 1993 Jun 30;193(3):1184-90
8323540
J Cancer Res Clin Oncol. 1993;119(9):549-54
8392076
Int J Cancer. 1993 Sep 9;55(2):213-9
8370618
Nat Genet. 1994 Aug;7(4):536-40
7951326
Dis Colon Rectum. 1995 Jan;38(1):64-7; discussion 67-8
7813348
Eur J Cancer Prev. 1994 Nov;3(6):473-9
7858479
J Natl Cancer Inst. 1995 Feb 15;87(4):265-73
7707417
Nat Genet. 1995 May;10(1):111-3
7647779
Cancer Epidemiol Biomarkers Prev. 1995 Oct-Nov;4(7):709-14
8672986
Cancer Res. 1996 Nov 1;56(21):4862-4
8895734
Anticancer Res. 1997 Jan-Feb;17(1A):429-32
9066689
Am J Epidemiol. 1996 Dec 1;144(11):1005-14
8942430