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Dietary Folate, Alcohol, and B Vitamins in Relation to LINE-1 Hypomethylation in Colon Cancer
  1. Eva S Schernhammer1,*,
  2. Edward Giovannucci2,
  3. Takako Kawasaki3,
  4. Bernard Rosner1,
  5. Charles Fuchs1,
  6. Shuji Ogino2
  1. 1 Channing Laboratory, United States;
  2. 2 Harvard School of Public Health, United States;
  3. 3 Dana-Farber Cancer Institute, United States
  1. Correspondence to: Eva S. Schernhammer, Channing Laboratory, 181 Longwood Ave., Boston, 20115, United States; nhess{at}


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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