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

Permanent link
https://hdl.handle.net/10037/33118
DOI
https://doi.org/10.1038/s41416-023-02164-7
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Accepted manuscript version (PDF)
Date
2023-02-09
Type
Journal article
Tidsskriftartikkel
Peer reviewed

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

Publisher
Springer Nature
Citation
Aglago, Cross, Riboli, Fedirko, Hughes, Fournier, Jakszyn, Freisling, Gunter, Dahm, Overvad, Tjønneland, Kyrø, Boutron-Ruault, Rothwell, Severi, Katzke, Srour, Schulze, Wittenbecher, Palli, Sieri, Pasanisi, Tumino, Ricceri, Bueno-de-Mesquita, Derksen, Skeie, Jensen, Lukic, Sánchez, Amiano, Colorado-Yohar, Barricarte, Ericson, van Guelpen, Papier, Knuppel, Casagrande, Huybrechts, Heath, Tsilidis, Jenab. Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study. British Journal of Cancer. 2023;128(8):1529-1540
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