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
N1 - Funding Information:
The authors would like to thank the EPIC study participants and staff for their valuable contribution to this research. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology, ICO (Spain); Swedish Cancer Society, Swedish Research Council, Region Skåne and Region Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom). VF is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the paper.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
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.
KW - Cancer
KW - Risk factors
UR - http://www.scopus.com/inward/record.url?scp=85147694973&partnerID=8YFLogxK
UR - https://www.webofscience.com/wos/woscc/full-record/WOS:000962948100002
U2 - https://www.nature.com/articles/s41416-023-02164-7
DO - https://www.nature.com/articles/s41416-023-02164-7
M3 - Article
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 -
