Global DNA hypomethylation (LINE-1) in the normal colon and lifestyle characteristics and dietary and genetic factors.
BACKGROUND
Global loss of methylated cytosines in DNA, thought to predispose to chromosomal instability and aneuploidy, has been associated with an increased risk of colorectal neoplasia. Little is known about the relationships between global hypomethylation and lifestyle, demographics, dietary measures, and genetic factors.


METHODS
Our data were collected as part of a randomized clinical trial testing the efficacy of aspirin and folic acid for the prevention of colorectal adenomas. At a surveillance colonoscopy approximately 3 years after the qualifying exam, we obtained two biopsies of the normal-appearing mucosa from the right colon and two biopsies from the left colon. Specimens were assayed for global hypomethylation using a pyrosequencing assay for LINE-1 (long interspersed nucleotide elements) repeats.


RESULTS
The analysis included data from 388 subjects. There was relatively little variability in LINE methylation overall. Mean LINE-1 methylation levels in normal mucosa from the right bowel were significantly lower than those on the left side (P < 0.0001). No significant associations were found between LINE-1 methylation and folate treatment, age, sex, body mass index, smoking status, alcohol use, dietary intake, or circulating levels of B vitamins, homocysteine, or selected genotypes. Race, dietary folic acid, and plasma B(6) showed associations with global methylation that differed between the right and the left bowel. The effect of folic acid on risk of adenomas did not differ according to extent of LINE-1 methylation, and we found no association between LINE-1 methylation and risk of adenomas.


CONCLUSIONS
LINE-1 methylation is not influenced by folic acid supplementation but differs by colon subsite.
Figueiredo
Jane C
JC
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. janefigu@usc.edu
Grau
Maria V
MV
Wallace
Kristin
K
Levine
A Joan
AJ
Shen
Lanlan
L
Hamdan
Randala
R
Chen
Xinli
X
Bresalier
Robert S
RS
McKeown-Eyssen
Gail
G
Haile
Robert W
RW
Baron
John A
JA
Issa
Jean-Pierre J
JP