Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

Abstract

This is a narrative review of the evidence supporting vitamin D’s anticancer actions. The first section reviews the findings from ecological studies of cancer with respect to indices of solar radiation, which found a reduced risk of incidence and mortality for approximately 23 types of cancer. Meta-analyses of observational studies reported the inverse correlations of serum 25-hydroxyvitamin D [25(OH)D] with the incidence of 12 types of cancer. Case-control studies with a 25(OH)D concentration measured near the time of cancer diagnosis are stronger than nested case-control and cohort studies as long follow-up times reduce the correlations due to changes in 25(OH)D with time. There is no evidence that undiagnosed cancer reduces 25(OH)D concentrations unless the cancer is at a very advanced stage. Meta-analyses of cancer incidence with respect to dietary intake have had limited success due to the low amount of vitamin D in most diets. An analysis of 25(OH)D-cancer incidence rates suggests that achieving 80 ng/mL vs. 10 ng/mL would reduce cancer incidence rates by 70 ± 10%. Clinical trials have provided limited support for the UVB-vitamin D-cancer hypothesis due to poor design and execution. In recent decades, many experimental studies in cultured cells and animal models have described a wide range of anticancer effects of vitamin D compounds. This paper will review studies showing the inhibition of tumor cell proliferation, dedifferentiation, and invasion together with the sensitization to proapoptotic agents. Moreover, 1,25-(OH)2D3 and other vitamin D receptor agonists modulate the biology of several types of stromal cells such as fibroblasts, endothelial and immune cells in a way that interferes the apparition of metastases. In sum, the available mechanistic data support the global protective action of vitamin D against several important types of cancer.

An Exploration of How Solar Radiation Affects the Seasonal Variation of Human Mortality Rates and the Seasonal Variation in Some Other Common Disorders

“…Whether these risks are affected by the environmental factors identified above as those which have the greatest increases in mortality risks through CVD and respiratory illness (ambient temperature, atmospheric particulates, UVB production of vitamin D or other effects, or NO produced by UVA) is mostly unknown, though low 25(OH)D concentration has been considered a risk factor for each. A noteworthy feature of the diseases listed in this table is that only cancers have been found to have highly significant inverse correlations between incidence and mortality rates and solar UVB doses in mid-latitude countries [100], and it shows very little seasonal variation in mortality rates. Even though cancers develop slowly, serum 25(OH)D concentrations measured near the time of diagnosis are more strongly correlated with incidence than are concentrations measured more than a few months [111] or years [100] prior to diagnosis.…”

“…A noteworthy feature of the diseases listed in this table is that only cancers have been found to have highly significant inverse correlations between incidence and mortality rates and solar UVB doses in mid-latitude countries [100], and it shows very little seasonal variation in mortality rates. Even though cancers develop slowly, serum 25(OH)D concentrations measured near the time of diagnosis are more strongly correlated with incidence than are concentrations measured more than a few months [111] or years [100] prior to diagnosis. Although RCTs have not found that supplementing with vitamin D reduces cancer incidence, it does reduce cancer mortality rates [101].…”

“…As reported by Marti-Soler and colleagues [1], cancer mortality rates do not have significant seasonal variations. Unlike CVD and respiratory tract infections, cancer mortality rates have significant inverse correlations with solar UVB in ecological studies [100]. Clinical trials have confirmed that vitamin D supplementation reduces the risk of cancer mortality [101].…”

“…Vitamin D deficiency is associated with increased colorectal cancer risks that appear likely to be causal [100]. Breast cancer survival is increased in people diagnosed in summer or autumn rather than in winter, although whether that is influenced by temperature, by vitamin D or by hormonal factors is unclear [107,108].…”

Vitamin D Status and Parkinson’s Disease

“…Its effects on inflammation (e.g., through inhibition of prostaglandins synthesis, p38 MAPK, and NF-kb signaling), DNA damage repair (e.g., through upregulation of p53, ATM, BRCA1 and other damage repair proteins), modulation of proliferation and differentiation (e.g., through upregulation of CDK inhibitors, activation of FOXO3/4, TGFB signaling), apoptosis, and autophagy are widely recognized. Among these several actions, calcitriol exerts a role in WNT–β-catenin signalling in colon cancer, in estrogens synthesis and signalling in estrogen receptor-positive (ER+) postmenopausal breast cancer, and, moreover, in androgen receptor (AR) signalling in prostate cancer [ 95 ].…”