Circulating 25-hydroxyvitamin D concentration and cause-specific mortality in the Melbourne Collaborative Cohort Study

Alicia K. Heath, Allison M. Hodge, Peter R. Ebeling, David Kvaskoff, Darryl W. Eyles, Graham G. Giles, Dallas R. English, Elizabeth J. Williamson

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Vitamin D deficiency is associated with higher all-cause mortality, but associations with specific causes of death are unclear. We investigated the association between circulating 25-hydroxyvitamin D (25(OH)D) concentration and cause-specific mortality using a case-cohort study within the Melbourne Collaborative Cohort Study (MCCS). Eligibility for the case-cohort study was restricted to participants with baseline dried blood spot samples and no pre-baseline diagnosis of cancer. These analyses included participants who died (n = 2307) during a mean follow-up of 14 years and a sex-stratified random sample of eligible cohort participants (‘subcohort’, n = 2923). Concentration of 25(OH)D was measured using liquid chromatography-tandem mass spectrometry. Cox regression, with Barlow weights and robust standard errors to account for the case-cohort design, was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cause-specific mortality in relation to 25(OH)D concentration with adjustment for confounders. Circulating 25(OH)D concentration was inversely associated with risk of death due to cancer (HR per 25 nmol/L increment = 0.88, 95 % CI 0.78–0.99), particularly colorectal cancer (HR = 0.75, 95 % CI 0.57–0.99). Higher 25(OH)D concentrations were also associated with a lower risk of death due to diseases of the respiratory system (HR = 0.62, 95 % CI 0.43–0.88), particularly chronic obstructive pulmonary disease (HR = 0.53, 95 % CI 0.30–0.94), and diseases of the digestive system (HR = 0.44, 95 % CI 0.26–0.76). Estimates for diabetes mortality (HR = 0.64, 95 % CI 0.33–1.26) and cardiovascular disease mortality (HR = 0.90, 95 % CI 0.76–1.07) lacked precision. The findings suggest that vitamin D might be important for preventing death due to some cancers, respiratory diseases, and digestive diseases.

Original languageEnglish
Article number105612
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Publication statusPublished - Apr 2020


  • 25-hydroxyvitamin D
  • Cancer mortality
  • Cardiovascular mortality
  • Mortality
  • Respiratory disease mortality
  • Vitamin D

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