Paper
Dietary Folate, Alcohol, and B Vitamins in Relation to LINE-1 Hypomethylation in Colon Cancer
1 Channing Laboratory, United States;
2 Harvard School of Public Health, United States;
3 Dana-Farber Cancer Institute, United States
Correspondence to: Eva S. Schernhammer, Channing Laboratory, 181 Longwood Ave., Boston, 20115, United States; nhess{at}channing.harvard.edu
Accepted 22 August 2009
Introduction: Although critical for methylation reactions, how dietary folate and B vitamins affect global DNA methylation level in colon 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.
Materials and methods: We examined the association between dietary intake of folate, alcohol, and B vitamins and LINE-1 hypomethylation in 609 incident colon cancers, utilizing the database of two independent prospective cohort studies.
Results: Participants with 
400µg folate intake per day were significantly less likely to develop LINE-1 hypomethylated colon cancers than those reporting <200µg of folate intake per day (Relative risk (RR)=0.57, 95% confidence interval (CI)=0.36-0.91) for <55% LINE-1 methylated colon tumors; RR=0.74, 95% CI=0.51-1.06 for 55-64% LINE-1 methylated colon tumors; and RR=1.08, 95% CI=0.66-1.75 for 65% LINE-1 methylated tumors; Pinteraction=0.01). By contrast, high alcohol consumption conferred a higher risk of LINE-1 hypomethylated cancers (15g alcohol per day versus none, RR=1.67, 95% CI=1.04-2.67 for <55% LINE1 methylated tumors; and RR=1.55, 95% CI=1.10-2.18 for 55-64% LINE-1 methylated tumors) but had no association with 65% LINE-1 methylated tumors (RR=1.06, 95% CI=0.69-1.62). High intakes of vitamin B6, B12, or methionine were not significantly associated with colon cancers, regardless of LINE-1 methylation level.
Conclusion: The influence of dietary folate intake and alcohol consumption on colon cancer risk differs significantly according to tumoral LINE-1 methylation level.
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