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

Abstract

There has been substantial enthusiasm recently regarding the potential role of vitamin D in the primary and secondary prevention of cancer. Laboratory studies demonstrate a range of anticarcinogenic effects for vitamin D compounds, but human studies have yielded little consistent evidence supporting a protective association. Higher circulating levels of vitamin D (i.e., 25-hydroxyvitamin D or 25(OH)D) appear to be associated with reduced risk of colorectal and bladder malignancies, but higher risk of prostate and possibly pancreatic cancers, with no clear association for most other organ sites examined. Despite there being no official institutional recommendations regarding the use of vitamin D supplements for cancer prevention, screenings for vitamin D deficiency and vitamin D supplement use have increased substantially over the past decade. These widespread practices demonstrate that population sociobehavioral changes are often adopted before scientifically well-informed policies and recommendations are available. This review critically examines the currently available epidemiologic literature regarding the associations between circulating 25(OH)D, vitamin D supplementation, and vitamin D-related genetic variation and cancer risk and mortality, with a particular emphasis on prospective studies. We identify several important gaps in our scientific knowledge that should be addressed in order to provide sufficient reproducible data to inform evidence-based recommendations related to optimal 25(OH)D concentrations (and any role for vitamin D supplementation) for the primary and secondary prevention of cancer. With few exceptions, such recommendations cannot be made at this time.

Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark

“…Several other studies, both separate studies and meta‐analyses, have examined the association between vitamin D and cancer incidence. Like the present study, Skaaby et al .…”

“…In humans, exposure of the skin to sunlight largely determines the level of circulating vitamin D with a smaller contribution from dietary intake. In the past years, several epidemiological studies and meta‐analyses have examined the association between vitamin D and cancer reporting inconsistent results. The incidence of some cancer types such as colorectal cancer has generally shown inverse associations with vitamin D while for other cancer types such as prostate cancer, positive associations have been seen.…”

Vitamin D differentially regulates colon stem cells in patient‐derived normal and tumor organoids

“…These actions of calcitriol are the consequence of it binding to and activating vitamin D receptor (VDR), a member of the nuclear receptor superfamily that acts predominantly as a transcription factor modulating the expression of a high number of genes in a tissue-and cell-dependent fashion [2,3]. Epidemiological and preclinical studies suggest an association between vitamin D deficiency and inflammatory bowel diseases (IBD), various extraskeletal disorders, and several neoplasias, particularly colorectal cancer (CRC) [1,3,4]. Supporting this, experimental results in immortal carcinoma cell lines and animal models of CRC demonstrate a multilevel protective action of calcitriol and other VDR agonists [3,5].…”

Serum Bioavailable, Rather Than Total, 25‐hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival

“…(10) However, evidence linking vitamin D status to organ-specific cancer survival is sparse and has produced conflicting results between and within types of cancers. (10)(11)(12) Specific to liver cancer, few studies have been conducted. (12,13) The total 25-hydroxyvitamin D (25OHD) level in serum or plasma is used currently to assess vitamin D status in routine clinical practice.…”