Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study

Elom K. Aglago, Amanda J. Cross, Elio Riboli, Veronika Fedirko, David J. Hughes, Agnes Fournier, Paula Jakszyn, Heinz Freisling, Marc J. Gunter, Christina C. Dahm, Kim Overvad, Anne Tjønneland, Cecilie Kyrø, Marie Christine Boutron-Ruault, Joseph A. Rothwell, Gianluca Severi, Verena Katzke, Bernard Srour, Matthias B. Schulze, Clemens WittenbecherDomenico Palli, Sabina Sieri, Fabrizio Pasanisi, Rosario Tumino, Fulvio Ricceri, Bas Bueno-de-Mesquita, Jeroen W.G. Derksen, Guri Skeie, Torill Enget Jensen, Marko Lukic, Maria Jose Sánchez, Pilar Amiano, Sandra Colorado-Yohar, Aurelio Barricarte, Ulrika Ericson, Bethany van Guelpen, Keren Papier, Anika Knuppel, Corinne Casagrande, Inge Huybrechts, Alicia K. Heath, Konstantinos K. Tsilidis, Mazda Jenab*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive. Methods: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method. Results: Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99). Conclusions: Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.

Original languageEnglish
Pages (from-to)1529-1540
Number of pages12
JournalBritish Journal of Cancer
Volume128
Issue number8
DOIs
Publication statusPublished - 12 Apr 2023

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