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Concentration of folate in colorectal tissue biopsies predicts prevalence of adenomatous polyps
  1. Andrew Flood1,
  2. Joel B Mason2,
  3. Zhenhua Liu2,
  4. Brooks D Cash3,4,
  5. Arthur Schatzkin5,
  6. Philip S Schoenfeld6,
  7. Amanda J Cross5
  1. 1Division of Epidemiology and Community Health and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA
  2. 2Vitamins & Carcinogenesis Laboratory, USDA Human Nutrition Research Center on Ageing at Tufts University, Boston, Minnesota, USA
  3. 3Division of Gastroenterology, Uniformed Services University of Health Sciences, Bethesda, Maryland, USA
  4. 4Division of Gastroenterology, National Naval Medical Center, Bethesda, Maryland, USA
  5. 5Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
  6. 6Division of Gastroenterology, University of Michigan School of Medicine and Veterans Affairs Center for Excellence in Health Services Research, Ann Arbor, Michigan, USA
  1. Correspondence to Andrew Flood, Division of Epidemiology and Community Health, University of Minnesota, 1300 South Second Street, Suite 300, Minneapolis, MN 55454, USA; flood009{at}


Background and aims Folate has been implicated as a potential aetiological factor for colorectal cancer. Previous research has not adequately exploited concentrations of folate in normal colonic mucosal biopsies to examine the issue.

Methods Logistic regression models were used to estimate ORs and 95% CIs of adenoma according to the tissue concentration of folate using asymptomatic average-risk women (40–70 years) in a colorectal cancer screening study. Of the 1593 eligible women who were offered enrolment, 1483 (93%) participated. Colonoscopy was complete to the caecum in 98.7% (1463/1483) of the subjects, and normal colonic tissue biopsies were obtained from 813 (56%) of these, of whom 170 had at least one adenoma.

Results A marginal reduction in risk for proximal adenomas (OR 0.56, 95% CI 0.29 to 1.09) but not distal adenomas (OR 1.01, 95% CI 0.43 to 2.37) was observed among women in the highest quintile of tissue folate concentration. A significant reduction in risk for advanced adenoma was observed for women in the highest quintile of tissue folate concentration (OR 0.24, 95% CI 0.06 to 0.93). Defining the outcome as proximal adenomatous and/or hyperplastic polyps, statistically significant inverse associations with tissue concentrations of folate were also observed (OR 0.54, 95% CI 0.31 to 0.95 for quintile 5 vs quintile 1).

Conclusions These findings are consistent with the hypothesis that folate status of colonic mucosa is an exposure that is aetiologically important in determining the risk of particular molecular subtypes of colorectal cancer.

  • Adenoma
  • folic acid
  • DNA microsatellite instability
  • colon carcinogenesis
  • methylation

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  • Funding Research funded by National Institutes of Health grant K07 CA108910-01A1 (AF), National Institute of Health grant K23-DK-60040 (PSS) and an American Society for Gastrointestinal Endoscopy Career Development Award (PSS). The CONCeRN Study was funded by research grants from the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy as well as Intramural Research Program funds from the National Cancer Institute, Bethesda, MD.

  • Competing interests None.

  • Ethics approval The study protocols were approved by the human rights committee and institutional review boards at the National Naval Medical Center, Bethesda, MD and at the National Cancer Institute, Bethesda, MD.

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