Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
Office of the Director, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Danish Cancer Society Research Center, Diet, Genes and Environment, Copenhagen, Denmark; University of Copenhagen, Department of Public Health, Copenhagen, Denmark.
Danish Cancer Society Research Center, Diet, Genes and Environment, Copenhagen, Denmark; University of Århus, Department of Public Health, Århus, Denmark.
University of Århus, Department of Public Health, Århus, Denmark.
CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France.
CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France.
CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; School of Biological Sciences, Queens University of Belfast, Belfast, Northern Ireland.
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
Hyblean Association for Epidemiology Research, Italy.
Dipartimento Di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital, Turin, Italy.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Arctic University of Norway, Norway.
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway.
Department of Functional Biology, Faculty of Medicine, University of Oviedo, Asturias, Spain.
Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Spain.
CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain.
National Institute for Health Innovation, University of Auckland, New Zealand.
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France; Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
BACKGROUND: Higher dietary calcium consumption is associated with lower colorectal cancer (CRC) risk. However, little data are available on the association between circulating calcium concentrations and CRC risk.
OBJECTIVES: To explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies.
METHODS: Conditional logistic regression models were used to calculate multivariable-adjusted ORs and 95% CIs in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC; n-cases = 947, n-controls = 947) and the UK Biobank (UK-BB; n-cases = 2759, n-controls = 12,021) cohorts.
RESULTS: In EPIC, nonalbumin-adjusted total serum calcium (a proxy of free calcium) was not associated with CRC (OR: 0.94; 95% CI: 0.85, 1.03; modeled as continuous variable, per 1 mg/dL increase), colon cancer (OR: 0.93; 95% CI: 0.82, 1.05) or rectal cancer (OR: 1.01; 95% CI: 0.84, 1.20) risk in the multivariable adjusted model. In the UK-BB, serum ionized calcium (free calcium, most active form) was inversely associated with the risk of CRC (OR: 0.85; 95% CI: 0.76, 0.95; per 1 mg/dL) and colon cancer (OR: 0.78; 95% CI: 0.68, 0.90), but not rectal cancer (OR: 1.02; 95% CI: 0.83, 1.24) in multivariable adjusted models. Meta-analysis of EPIC and UK-BB CRC risk estimates showed an inverse risk association for CRC in the multivariable adjusted model (OR: 0.90; 95%CI: 0.84, 0.97). In analyses by quintiles, in both cohorts, higher levels of serum calcium were associated with reduced CRC risk (EPIC: ORQ5vs.Q1: 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: ORQ5vs.Q1: 0.82; 95% CI: 0.72, 0.94; P-trend < 0.01). Analyses by anatomical subsite showed an inverse cancer risk association in the colon (EPIC: ORQ5vs.Q1: 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: ORQ5vs.Q1: 0.75; 95% CI: 0.64, 0.88; P-trend < 0.01) but not the rectum.
CONCLUSIONS: In UK-BB, higher serum ionized calcium levels were inversely associated with CRC, but the risk was restricted to the colon. Total serum calcium showed a null association in EPIC. Additional prospective studies in other populations are needed to better investigate these associations.
Elsevier, 2023. Vol. 117, no 1, p. 33-45