Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer.
OBJECTIVE
Although critical for methylation reactions, how dietary folate and B vitamins affect global DNA methylation level in colorectal cancers is currently unknown. Long interspersed nucleotide element-1 (LINE-1) is an emerging indicator of genome-wide DNA methylation level that has previously been linked to colon cancer survival.


METHODS
We examined the association between dietary intake of folate, alcohol and B vitamins and LINE-1 hypomethylation in 609 incident colon cancers, utilising the database of two independent prospective cohort studies.


RESULTS
Participants with > or = 400 microg folate intake per day were significantly less likely to develop LINE-1 hypomethylated colon cancers than those reporting <200 microg of folate intake per day (RR=0.57, 95% CI=0.36 to 0.91 for <55% LINE-1 methylated colon tumours; RR=0.74, 95% CI=0.51 to 1.06 for 55-64% LINE-1 methylated colon tumours; and RR=1.08, 95% CI=0.66 to 1.75 for > or = 65% LINE-1 methylated tumours; P(interaction)=0.01). By contrast, high alcohol consumption conferred a higher risk of LINE-1 hypomethylated cancers (> or = 15 g alcohol per day versus none, RR=1.67, 95% CI=1.04 to 2.67 for <55% LINE1 methylated tumours; and RR=1.55, 95% CI=1.10 to 2.18 for 55-64% LINE-1 methylated tumours) but had no association with > or = 65% LINE-1 methylated tumours (RR=1.06, 95% CI=0.69 to 1.62). High intakes of vitamin B(6), B(12) or methionine were not significantly associated with colon cancers, regardless of LINE-1 methylation level.


CONCLUSIONS
The influence of dietary folate intake and alcohol consumption on colon cancer risk differs significantly according to tumoral LINE-1 methylation level.
Schernhammer
Eva S
ES
Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA. eva.schernhammer@channing.harvard.edu
Giovannucci
Edward
E
Kawasaki
Takako
T
Rosner
Bernard
B
Fuchs
Charles S
CS
Ogino
Shuji
S
D000428:Alcohol Drinking / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000517:prevention & control; D019175:DNA Methylation / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000235:genetics; D004032:Diet / Q000706:statistics & numerical data; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects / Q000235:genetics; D008297:Male; D011446:Prospective Studies; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000494:pharmacology*; D025101:Vitamin B 6 / Q000008:administration & dosage / Q000494:pharmacology*
D004273:DNA, Neoplasm; D000431:Ethanol; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12