Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control stu

Published 21 January 2010, doi:10.1136/bmj.b5500
Cite this as: BMJ 2010;340:b5500

Research
Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study

Mazda Jenab, scientist1, H Bas Bueno-de-Mesquita, senior scientist2,33, Pietro Ferrari, scientist1,3, Franzel J B van Duijnhoven, scientist2,4, Teresa Norat, principal research fellow5, Tobias Pischon, scientist6, Eugène H J M Jansen, scientist2, Nadia Slimani, scientist, group head1, Graham Byrnes, statistician1, Sabina Rinaldi, scientist1, Anne Tjønneland, department head7, Anja Olsen, scientist7, Kim Overvad, professor of epidemiology8, Marie-Christine Boutron-Ruault, senior scientist9, Françoise Clavel-Chapelon, department head9, Sophie Morois, research fellow9, Rudolf Kaaks, professor, division head10, Jakob Linseisen, unit head10,34, Heiner Boeing, professor, department chair6, Manuela M Bergmann, scientist6, Antonia Trichopoulou, professor of nutrition11,12, Gesthimani Misirli, research associate11, Dimitrios Trichopoulos, professor of cancer prevention, professor of epidemiology13, Franco Berrino, department chief14, Paolo Vineis, chair of environmental epidemiology, unit chief5,15, Salvatore Panico, professor of internal medicine, unit chief 16, Domenico Palli, unit chief17, Rosario Tumino, director18, Martine M Ros, junior scientist2,19, Carla H van Gils, associate professor of clinical epidemiology4, Petra H Peeters, professor of epidemiology4, Magritt Brustad, researcher20, Eiliv Lund, professor20, María-José Tormo, unit chief, scientist21,22, Eva Ardanaz, scientist23, Laudina Rodríguez, section chief24, Maria-José Sánchez, lecturer, director25,26, Miren Dorronsoro, unit chief27, Carlos A Gonzalez, scientist, unit chief28, Göran Hallmans, professor29, Richard Palmqvist, senior lecturer, consultant30, Andrew Roddam, visiting research fellow31, Timothy J Key, deputy director31, Kay-Tee Khaw, professor of clinical gerontology32, Philippe Autier, scientist, section head1, Pierre Hainaut, scientist, section head1, Elio Riboli, director5

1 International Agency for Research on Cancer (IARC-WHO), Lyon, France, 2 National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands , 3 Data Collection and Exposure Unit, European Food Safety Authority (EFSA), Parma, Italy, 4 Julius Centre for Health Sciences and Primary Care, University Medical Centre, Utrecht, Netherlands, 5 School of Public Health, Imperial College, London, UK, 6 Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany, 7 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark, 8 Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark, 9 Inserm (Institut National de la Santé et de la Recherche Médicale) ERI 20, EA 4045, and Institut Gustave Roussy, Villejuif, France, 10 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 11 Department of Hygiene and Epidemiology, University of Athens Medical School, Greece, 12 Hellenic Health Foundation, Greece, 13 Department of Epidemiology, Harvard School of Public Health, USA and Bureau of Epidemiologic Research, Academy of Athens, Greece , 14 Department of Preventive and Predictive Medicine, Etiologic Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Milan, Italy, 15 ISI Foundation, Turin, Italy, 16 Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy, 17 Molecular and Nutritional Epidemiology Unit, ISPO (Cancer Research and Prevention Institute), Florence, Italy, 18 Ragusa Cancer Registry and Histopathology Unit, "Civile M.P.Arezzo" Hospital, ASP 7 Ragusa, Italy, 19 Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 20 Centre for Sami Health Research, Institute of Community Medicine, University of Tromsø, Tromsø, Norway, 21 Epidemiology Service, Murcia Regional Health Authority, Spain, 22 CIBER Epidemiología y Salud Pública (CIBERESP), Spain, 23 Public Health Institute of Navarra, Pamplona, Spain. CIBER Epidemiología y Salud Pública (CIBERESP), Spain, 24 Health Information Section, Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain, 25 Andalusian School of Public Health-Granada (Spain), 26 CIBER Epidemiología y Salud Pública (CIBERESP), Spain, 27 Epidemiology Unit, Public Health Division of Guipuzkoa, San Sebastian, Spain, 28 Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain, 29 Department of Public Health and Clinical Medicine, Nutritional Research, Umeå, Sweden, 30 Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden, 31 Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK, 32 Clinical Gerontology Unit, University of Cambridge, Cambridge, UK, 33 Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands, 34 Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany

Correspondence to: M Jenab, Lifestyle and Cancer Group, International Agency for Research on Cancer, Lyon, France Jenab@iarc.fr

Objective: To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations.
Design Nested case-control study.

Setting: The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries.

Participants: 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls

Main outcome measures: Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders.

Results: 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); 100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation.

Conclusions: The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.

© Jenab et al 2010
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