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 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-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, 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
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
Publication status	Published - 12 Apr 2023

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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

@article{afe3d2c5da30496d91bf9a7112fd27bd,

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",

volume = "128",

pages = "1529--1540",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Springer Nature",

number = "8",

}

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

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.

UR - https://www.scopus.com/pages/publications/85147694973

U2 - 10.1038/s41416-023-02164-7

DO - 10.1038/s41416-023-02164-7

M3 - Article

C2 - 36759722

AN - SCOPUS:85147694973

SN - 0007-0920

VL - 128

SP - 1529

EP - 1540

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 8

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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