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Grand Rounds

Is There a Protective Association Between Vitamin D Levels and Cancer Risk?

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BACKGROUND AND PURPOSE:  

  • In vitro studies show that Vitamin D exerts antiproliferative and pro-differentiating effects on cancer cells through the various mechanisms 
  • Budhathoki et al. (BMJ, 2018) sought to determine whether pre-diagnostic circulating vitamin concentration is associated with  risk for overall and site-specific cancer 

METHODS:  

  • Nested case-cohort study  
  • Data obtained from the Japan Public Health Center-based Prospective Study cohort 
    • Prospective, ongoing population-based cohort study on the role of lifestyle and other factors and risk for cancers and chronic diseases  
    • All cohort members were followed from 1990 to 31 December 2009 
  • Plasma concentration of 25-hydroxyvitamin D was measured by enzyme immunoassay  
  • Participants were categorized and divided into quarters based on  
    • Sex   
    • Season specific distribution of 25-hydroxyvitamin D  
  • Multivariable adjusted hazard ratio calculations based on Cox proportional hazard models  
  • The lowest quarter was used as reference for overall and site specific cancer across categories of 25-hydroxyvitamin D concentrations  
  • The primary outcome was incidence of overall or site specific cancer 

RESULTS:  

  • Data was collected from 3301 incident cases of cancer and 4044 randomly selected subcohort participants  
  • Plasma 25-hydroxyvitamin D concentrations were inversely associated with risk of total cancer for the second to fourth quarters (P for trend = 0.001)  
    • 2nd quarter adjusted HR 0.81 (95% CI 0.70 to 0.94)  
    • 3rd quarter adjusted HR 0.75 (0.65 to 0.87)
    • 4th quarter adjusted HR 0.78 (0.67 to 0.91)  
  • An inverse association was found for liver cancer  (P for trend=0.006)
    • Corresponding hazard ratios of
    • 2nd quarter adjusted HR 0.70 (0.44 to 1.13)
    • 3rd quarter adjusted HR 0.65 (0.40 to 1.06)
    • 4th quarter adjusted HR 0.45 (0.26 to 0.79)
  • Subgroup analysis by sex did not demonstrate a significant difference between men and women

CONCLUSION:  

  • Major strength of this study was sample size and prospective, long-term follow-up 
  • The study was powered for overall cancer risk 
    • Numbers of different types of cancers were small and the study was not powered for many individual cancers  
    • The total cancer risk may be driven by accumulation of small effects over multiple different cancer types/sites  
  • Higher vitamin D concentrations were associated with lower risk of total cancer, including liver cancer  
  • The results from this study suggest that “raising a low 25-hydroxyvitamin D concentration to an intermediate concentration may provide protection, whereas raising it to a higher concentration (probably above around 80 nmol/L) may provide no further benefit” 
    • Further randomized trials would be required to confirm the conclusions of this study and whether there is a threshold above which there is no demonstrable benefit to increasing vitamin D levels  

Learn More – Primary Sources:  

Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort

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Related ObG Topics:

Does Vitamin D Intake Decrease the Risk for Gestational Diabetes Mellitus?
Does Vitamin D Decrease Risk of Respiratory Infections?
Do Vitamin D and Calcium Supplements Decrease Cancer Risk?

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