Higher vitamin D levels linked to lower cancer risk, but subject to 'ceiling effect': Japan cohort study
While vitamin D's bone health benefits have been well-researched, more recent studies have suggested it also protects against chronic diseases, including cancer.
In vitro studies have found that vitamin D has a pro-differentiating and an anti-proliferative impact on malignant cells due to its regulation of multiple signalling pathways involved in apoptosis, angiogenesis and inflammation.
In experimental animal models, the activation of the vitamin D endocrine axis by vitamin D itself or its analogues has been shown to restrict tumour development and progression on the breast, colon, prostate, and other tissues, implying that vitamin D has a chemo-preventive role in carcinogenesis.
Specific and overall focus
Researchers at Japan's National Cancer Center and Shiga University of Medical Science therefore sought to determine the relationship between pre-diagnostic circulating vitamin D concentration and the risk of overall and site-specific cancer.
They conducted a nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort, which involved nine public health centre areas across the country.
A total of 3,301 cancer patients and 4,044 randomly selected sub-cohort participants were recruited for the study. Their plasma concentration of 25-hydroxyvitamin D was measured, and they were divided into quarters based on sex- and season-specific distribution of vitamin D among the sub-cohorts.
The researchers subsequently observed that vitamin D concentration was inversely associated with the risk of total cancer, while the results for site-specific cancers showed an inverse association between vitamin D levels and liver cancer risk.
Furthermore, a sensitivity analysis found that alternately removing cases of cancer at specific sites from the total number of cancer cases "did not substantially change the overall hazard ratios".
They added that this showed that higher levels of vitamin D were linked to a lower risk of total cancer, and that their findings supported the hypothesis that vitamin D is able to protect against cancers at numerous sites.
A ceiling effect
Despite their observation that a higher circulating concentration of vitamin D was linked to a lower risk of subsequent cancer, the researchers concluded: "Nevertheless, the lower risk associated with higher circulating vitamin D concentration seemed to show a ceiling effect, which may suggest that although maintaining an optimal 25-hydroxyvitamin D concentration is important for (the) prevention of cancer, having a concentration beyond this optimal level may provide no further benefit.
"Future studies are needed to clarify the dose-response pattern and the optimal concentrations for cancer prevention."
Source: The British Medical Journal
http://dx.doi.org/10.1136/bmj.k671
"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"
Authors: Sanjeev Budhathoki, et al.
