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 Wittenbecher; Domenico 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

doi:10.1038/s41416-023-02164-7

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

Epidemiology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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, HR_Q5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HR_Q5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HR_Q5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HR_Q5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HR_Q5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HR_Q5vs.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 language	English (US)
Pages (from-to)	1529-1540
Number of pages	12
Journal	British journal of cancer
Volume	128
Issue number	8
DOIs	https://doi.org/10.1038/s41416-023-02164-7
State	Published - Apr 12 2023

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1038/s41416-023-02164-7

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Aglago, E. K., Cross, A. J., Riboli, E., Fedirko, V., Hughes, D. J., Fournier, A., Jakszyn, P., Freisling, H., Gunter, M. J., Dahm, C. C., Overvad, K., Tjønneland, A., Kyrø, C., Boutron-Ruault, M. C., Rothwell, J. A., Severi, G., Katzke, V., Srour, B., Schulze, M. B., ... Jenab, M. (2023). 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, 128(8), 1529-1540. https://doi.org/10.1038/s41416-023-02164-7

Aglago, EK, Cross, AJ, Riboli, E, Fedirko, V, Hughes, DJ, Fournier, A, Jakszyn, P, Freisling, H, Gunter, MJ, Dahm, CC, Overvad, K, Tjønneland, A, Kyrø, C, Boutron-Ruault, MC, Rothwell, JA, Severi, G, Katzke, V, Srour, B, Schulze, MB, Wittenbecher, C, Palli, D, Sieri, S, Pasanisi, F, Tumino, R, Ricceri, F, Bueno-de-Mesquita, B, Derksen, JWG, Skeie, G, Jensen, TE, Lukic, M, Sánchez, MJ, Amiano, P, Colorado-Yohar, S, Barricarte, A, Ericson, U, van Guelpen, B, Papier, K, Knuppel, A, Casagrande, C, Huybrechts, I, Heath, AK, Tsilidis, KK & Jenab, M 2023, '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, vol. 128, no. 8, pp. 1529-1540. https://doi.org/10.1038/s41416-023-02164-7

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2023",

month = apr,

day = "12",

doi = "10.1038/s41416-023-02164-7",

language = "English (US)",

volume = "128",

pages = "1529--1540",

journal = "British journal of cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "8",

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TY - JOUR

T1 - Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study

AU - Aglago, Elom K.

AU - Cross, Amanda J.

AU - Riboli, Elio

AU - Fedirko, Veronika

AU - Hughes, David J.

AU - Fournier, Agnes

AU - Jakszyn, Paula

AU - Freisling, Heinz

AU - Gunter, Marc J.

AU - Dahm, Christina C.

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Kyrø, Cecilie

AU - Boutron-Ruault, Marie Christine

AU - Rothwell, Joseph A.

AU - Severi, Gianluca

AU - Katzke, Verena

AU - Srour, Bernard

AU - Schulze, Matthias B.

AU - Wittenbecher, Clemens

AU - Palli, Domenico

AU - Sieri, Sabina

AU - Pasanisi, Fabrizio

AU - Tumino, Rosario

AU - Ricceri, Fulvio

AU - Bueno-de-Mesquita, Bas

AU - Derksen, Jeroen W.G.

AU - Skeie, Guri

AU - Jensen, Torill Enget

AU - Lukic, Marko

AU - Sánchez, Maria Jose

AU - Amiano, Pilar

AU - Colorado-Yohar, Sandra

AU - Barricarte, Aurelio

AU - Ericson, Ulrika

AU - van Guelpen, Bethany

AU - Papier, Keren

AU - Knuppel, Anika

AU - Casagrande, Corinne

AU - Huybrechts, Inge

AU - Heath, Alicia K.

AU - Tsilidis, Konstantinos K.

AU - Jenab, Mazda

PY - 2023/4/12

Y1 - 2023/4/12

N2 - 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.

AB - 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.

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SN - 0007-0920

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JO - British journal of cancer

JF - British journal of cancer

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ER -

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

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