Vitamin D and Colorectal, Breast, and Prostate Cancers: A Review of the Epidemiological Evidence

Abstract

Over the past two decades, the question of whether vitamin D has a role in cancer incidence, progression, and mortality has been studied in detail. Colorectal, breast, and prostate cancers have been a particular area of focus; together, these three malignancies account for approximately 35% of cancer cases and 20% of cancer deaths in the United States, and as such are a major public health concern. Herein, we review and synthesize the epidemiological research regarding vitamin D, as measured by the biomarker 25-hydroxycholecalciferol [25(OH)D], and the incidence, progression, and mortality of these cancers. Overall, the results of observational studies of the relationship between 25(OH)D and colorectal cancer have revealed a consistent inverse association for incidence and mortality; while for breast cancer, results have generally demonstrated a relationship between higher 25(OH)D and lower risk for progression and mortality. In contrast, randomized, double-blind clinical trials conducted to date have generally failed to support these findings. For prostate cancer, there is no convincing evidence of an association between 25(OH)D and incidence, and inconsistent data for progression and mortality, though results of one open label clinical trial suggest that supplementation with 4000 IU/d of vitamin D3 may inhibit progression of the disease. Nonetheless, until the results of additional ongoing randomized, double-blind clinical trials are reported, it will be difficult to ascertain if vitamin D itself is related to a reduction in risk for some cancer endpoints, or whether high concentrations of the vitamin D biomarker 25(OH)D may instead serve as a marker for an overall beneficial risk factor profile.

Vitamin D and Cancer Risk and Mortality: State of the Science, Gaps, and Challenges

“…Interestingly, 1 recent study found that a higher vitamin D status was more beneficial for colorectal tumors having greater lymphocytic infiltration (138), supporting the view expressed in a recent commentary that substantially greater attention is needed with respect to organ site-specific biological mechanisms (139). The current literature also suggests that there may be other important factors that interact with vitamin D status, such as menopausal status in breast cancer (17), sex in colorectal cancer (140), and circulating vitamin D binding protein in prostate cancer (141). Relevant to the latter observation, studies have begun to pay more attention to the measurement of 25(OH)D by examining the role of free versus total vitamin D in cancer etiology, with free 25(OH)D appearing to be more important for some cancer sites and total 25(OH)D appearing to be more important for others (12,80,(141)(142)(143) (145).…”

Serum 25-hydroxyvitamin D concentrations in dogs with osteosarcoma do not differ from those of age- and weight-matched control dogs

“…Epidemiologic studies by Apperly (1941) identified an inverse correlation between sun exposure and cancer risk in people. This spurred further research, which identified an association between decreased 25-hydroxyvitamin D (25[OH]D) concentrations and an increased risk of certain tumor types such as colonic, prostatic, and mammary cancers (Jacobs et al, 2016). Veterinary researchers have identified an increased overall risk of cancer, mast cell tumor, lymphoma, and malignant hemoabdomen in dogs with significantly lower 25(OH)D (Gerber et al, 2004;Mellanby, 2016;Selting et al, 2016).…”

Greater Adherence to Cancer Prevention Guidelines Is Associated with Higher Circulating Concentrations of Vitamin D Metabolites in a Cross-Sectional Analysis of Pooled Participants from 2 Chemoprevention Trials

“…These guidelines are consistent with recommendations for the prevention of other major diseases as well, and, if followed, are associated with healthier lives overall (42)(43)(44). To our knowledge, no studies have assessed the relation between ACS guidelines for cancer prevention and circulating concentrations of vitamin D metabolites, which are biomarkers often linked to health outcomes (45). This current work offers evidence indicating that greater adherence to an overall lifestyle pattern as outlined by the ACS nutrition and physical activity cancer prevention guidelines is associated with higher concentrations of both 25(OH)D and 1,25(OH) 2 D, based on a pooled sample of participants enrolled in one of 2 chemoprevention trials in Arizona.…”