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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