Heme Iron Intake, Dietary Antioxidant Capacity, and Risk of Colorectal Adenomas in a Large Cohort Study of French Women

Cancer Epidemiol Biomarkers Prev. 2016 Apr;25(4):640-7. doi: 10.1158/1055-9965.EPI-15-0724. Epub 2016 Jan 28.


Background: Nitrosylated and non-nitrosylated heme iron from red processed and nonprocessed meat have been associated with increased colorectal carcinogenesis. Mechanisms include oxidative processes. It has been hypothesized that dietary antioxidants could counteract the effects of heme iron. We investigated the relationships between heme iron intake and the risk of colorectal adenomas, and a potential interaction with the dietary antioxidant capacity, in the E3N prospective cohort study.

Methods: The study included 17,397 women, who underwent at least one colonoscopy. Among them, 1,409 were diagnosed with at least one first colorectal adenoma during the 103,253 person-years of follow-up. Dietary intake was measured by a semiquantitative food history questionnaire. HR estimates and 95% confidence intervals (CI) were obtained from Cox proportional hazards models, adjusted for potential confounders.

Results: Heme iron intake was positively associated with colorectal and colon adenoma risks [HR for the fourth vs. first quartile: HR4 = 1.36 (1.13-1.65), Ptrend = 0.001 and HR4 = 1.49; 95% CI, 1.19-1.87; Ptrend = 0.0003, respectively]. Nonnitrosylated and nitrosylated heme iron intakes were, respectively, associated with advanced distal and proximal adenoma risks. There was a dose-effect relationship between the heme iron to total dietary antioxidant capacity ratio and colorectal adenoma risk.

Conclusion: In this prospective cohort study, the association between heme iron and colorectal adenoma risk was found to depend on site, nitrosylation or not, and the ratio with the NEAC.

Impact: These results emphasize the need for a global assessment of diet when considering nutritional prevention of colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 25(4); 640-7. ©2016 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / diagnosis*
  • Adenoma / pathology
  • Antioxidants
  • Cohort Studies
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / pathology
  • Female
  • France
  • Heme / adverse effects*
  • Humans
  • Iron, Dietary / adverse effects*
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Surveys and Questionnaires


  • Antioxidants
  • Iron, Dietary
  • Heme