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Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer
  1. Eva S Schernhammer1,2,3,
  2. Edward Giovannucci2,
  3. Takako Kawasaki4,
  4. Bernard Rosner1,
  5. Charles S Fuchs1,4,
  6. Shuji Ogino2,4,5
  1. 1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  2. 2Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
  3. 3Ludwig Boltzmann-Institute for Applied Cancer Research, KFJ-Spital, Vienna, Austria and Applied Cancer Research – Institution for Translational Research Vienna (ACR–ITR Vienna), Austria
  4. 4Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
  5. 5Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Eva S Schernhammer, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA; eva.schernhammer{at}


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 ≥400 μg folate intake per day were significantly less likely to develop LINE-1 hypomethylated colon cancers than those reporting <200 μg 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 ≥65% LINE-1 methylated tumours; Pinteraction=0.01). By contrast, high alcohol consumption conferred a higher risk of LINE-1 hypomethylated cancers (≥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 ≥65% LINE-1 methylated tumours (RR=1.06, 95% CI=0.69 to 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.

  • Methylgroup donors
  • folate
  • vitamin B6
  • colorectal cancer
  • DNA methylation
  • colorectal cancer

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  • The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

  • Funding This work is supported by National Institutes of Health research grants CA70817, CA87969, CA55075, CA42812, CA58684, CA90598, CA122826, the Bennett Family Fund and Entertainment Industry Foundation, and the Entertainment Industry Foundation National Colorectal Cancer Research Alliance (NCCRA).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the BWH.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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