European Journal of Epidemiology

, Volume 33, Issue 11, pp 1087–1099 | Cite as

Circulating 25-hydroxyvitamin D up to 3 decades prior to diagnosis in relation to overall and organ-specific cancer survival

  • Stephanie J. WeinsteinEmail author
  • Alison M. Mondul
  • Kai Yu
  • Tracy M. Layne
  • Christian C. Abnet
  • Neal D. Freedman
  • Racheal Z. Stolzenberg-Solomon
  • Unhee Lim
  • Mitchell H. Gail
  • Demetrius Albanes


While vitamin D has been associated with improved overall cancer survival in some investigations, few have prospectively evaluated organ-specific survival. We examined the accepted biomarker of vitamin D status, serum 25-hydroxyvitamin D [25(OH)D], and cancer survival in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Of 4616 cancer cases with measured serum 25(OH)D, 2884 died of their cancer during 28 years of follow-up and 1732 survived or died of other causes. Proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between pre-diagnostic 25(OH)D and overall and site-specific survival. Serum 25(OH)D was significantly lower among cases who subsequently died from their malignancy compared with those who did not (medians 34.7 vs. 36.5 nmol/L, respectively; p = 0.01). Higher 25(OH)D was associated with lower overall cancer mortality (HR = 0.76, 95% CI 0.67–0.85 for highest vs. lowest quintile, p-trend < 0.0001). Higher 25(OH)D was related to lower mortality from the following site-specific malignancies: prostate (HR = 0.74, 95% CI 0.55–1.01, p-trend = 0.005), kidney (HR = 0.59, 95% CI 0.35–0.98, p-trend = 0.28), and melanoma (HR = 0.39, 95% CI 0.20–0.78, p-trend = 0.01), but increased mortality from lung cancer (HR = 1.28, 95% CI 1.02–1.61, p-trend = 0.19). Improved survival was also suggested for head and neck, gastric, pancreatic, and liver cancers, though not statistically significantly, and case numbers for the latter two organ sites were small. Higher 25(OH)D status years prior to diagnosis was related to improved survival for overall and some site-specific cancers, associations that should be examined in other prospective populations that include women and other racial-ethnic groups.


Vitamin D Cancer Mortality Survival analysis Prospective cohort 



25-hydroxyvitamin D


Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study


Body mass index


Confidence intervals


Hazard ratio


International classification of diseases



The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, and by U.S. Public Health Service contract HHSN261201500005C from the National Cancer Institute, Department of Health and Human Services.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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Authors and Affiliations

  1. 1.Division of Cancer Epidemiology and GeneticsNational Cancer Institute, NIH, Department of Health and Human ServicesBethesdaUSA
  2. 2.Department of Epidemiology, School of Public HealthUniversity of MichiganAnn ArborUSA
  3. 3.Cancer Epidemiology ProgramUniversity of Hawaii Cancer CenterHonoluluUSA

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