Abstract
BACKGROUND AND AIMS: 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. CONCLUSION: The influence of dietary folate intake and alcohol consumption on colon cancer risk differs significantly according to tumoral LINE-1 methylation level.