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

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  • Mazda Jenab, Denmark
  • H Bas Bueno-de-Mesquita, Denmark
  • Pietro Ferrari, Denmark
  • Franzel J B van Duijnhoven, Denmark
  • Teresa Norat, Denmark
  • Tobias Pischon, Denmark
  • Eugène H J M Jansen, Denmark
  • Nadia Slimani, Denmark
  • Graham Byrnes, Denmark
  • Sabina Rinaldi, Denmark
  • Anne Tjønneland, Denmark
  • Anja Olsen
  • Kim Overvad
  • Marie-Christine Boutron-Ruault, Denmark
  • Françoise Clavel-Chapelon, Denmark
  • Sophie Morois, Denmark
  • Rudolf Kaaks, Denmark
  • Jakob Linseisen, Denmark
  • Heiner Boeing, Denmark
  • Manuela M Bergmann, Denmark
  • Antonia Trichopoulou, Denmark
  • Gesthimani Misirli, Denmark
  • Dimitrios Trichopoulos, Denmark
  • Franco Berrino, Denmark
  • Paolo Vineis, Denmark
  • Salvatore Panico, Denmark
  • Domenico Palli, Denmark
  • Rosario Tumino, Denmark
  • Martine M Ros, Denmark
  • Carla H van Gils, Denmark
  • Petra H Peeters, Denmark
  • Magritt Brustad, Denmark
  • Eiliv Lund, Denmark
  • María-José Tormo, Denmark
  • Eva Ardanaz, Denmark
  • Laudina Rodríguez, Denmark
  • Maria-José Sánchez, Denmark
  • Miren Dorronsoro, Denmark
  • Carlos A Gonzalez, Denmark
  • Göran Hallmans, Denmark
  • Richard Palmqvist, Denmark
  • Andrew Roddam, Denmark
  • Timothy J Key, Denmark
  • Kay-Tee Khaw, Denmark
  • Philippe Autier, Denmark
  • Pierre Hainaut, Denmark
  • Elio Riboli, Denmark
  • Institute of Epidemiology and Social Medicine
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); >or=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.
Original languageEnglish
JournalB M J
Pages (from-to)b5500
Publication statusPublished - 21 Jan 2010

    Research areas

  • Calcium, Case-Control Studies, Colorectal Neoplasms, Diet, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Europe, Female, Humans, Life Style, Male, Middle Aged, Risk Factors, Vitamin D

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