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