Molecular Link between Vitamin D and Cancer Prevention

Abstract

The metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (also known as calcitriol), is a biologically active molecule required to maintain the physiological functions of several target tissues in the human body from conception to adulthood. Its molecular mode of action ranges from immediate nongenomic responses to longer term mechanisms that exert persistent genomic effects. The genomic mechanisms of vitamin D action rely on cross talk between 1α,25-dihydroxyvitamin D3 signaling pathways and that of other growth factors or hormones that collectively regulate cell proliferation, differentiation and cell survival. In vitro and in vivo studies demonstrate a role for vitamin D (calcitriol) in modulating cellular growth and development. Vitamin D (calcitriol) acts as an antiproliferative agent in many tissues and significantly slows malignant cellular growth. Moreover, epidemiological studies have suggested that ultraviolet-B exposure can help reduce cancer risk and prevalence, indicating a potential role for vitamin D as a feasible agent to prevent cancer incidence and recurrence. With the preventive potential of this biologically active agent, we suggest that countries where cancer is on the rise—yet where sunlight and, hence, vitamin D may be easily acquired—adopt awareness, education and implementation strategies to increase supplementation with vitamin D in all age groups as a preventive measure to reduce cancer risk and prevalence.

All sites but skin cancer incidences analyzed worldwide by sex, age, and skin type over time (1955-2007), advancing age, and UVB dose reveals important carcinogenic drivers

“…[15] We found breast, prostate and colon cancers decrease with increasing UVB dose (or increasing latitude), which agrees with others who found breast, [70] prostate [71] and colon [72] cancers decrease with increasing UVB dose, [73] decreasing latitude [74] or increasing vitamin D 3 . [75] We expanded on those findings by analyzing the different skin types in five age groups to find only the whites, but not the blacks, oldest age group (70-85+) have significant negative slopes.…”

“…We found only the cancer incidences in developed countries primarily of European ancestry (see Figure 1), as noted by the New Zealand profiles compared to the developing country with eastern Indian profiles, are steadily increasing over time and they are also affected by vitamin D 3 (breast and prostate). [15] However, when we analyzed all cancer incidences over UVB dose, we did not find significant support for a role for vitamin D because the slope of the line was not significant with UVB dose for most age groups except the oldest (results not shown). While almost 20 cancers appear to decrease with decreasing UVB dose or increasing vitamin D levels, [15] some cancers increase with increasing UVB [12] so that a mixture of these cancers might obscure a relationship with UVB dose.…”

“…[15] However, when we analyzed all cancer incidences over UVB dose, we did not find significant support for a role for vitamin D because the slope of the line was not significant with UVB dose for most age groups except the oldest (results not shown). While almost 20 cancers appear to decrease with decreasing UVB dose or increasing vitamin D levels, [15] some cancers increase with increasing UVB [12] so that a mixture of these cancers might obscure a relationship with UVB dose. For example, the incidence of cervical or pharyngeal cancers increase with increasing UVB dose in the US only in whites, and not blacks, presumably from inflammatory cytokine production and the fact that these cells apparently lack the vitamin D receptor and corresponding apoptotic mechanism.…”

“…[13] In contrast, UVB produces vitamin D 3 in the skin [14] that also circulates systemically and may counter the effects of the inflammatory cytokines and possibly even decrease the risk for getting some cancers. [15] UVA radiation creates ROS that can further contribute toward carcinogenesis by activating HPV [16] and combined with estrogen cause increased expression of HPV's oncogenic proteins E6 and E7 [17] that immortalize cells by inactivating p53 and pRB, respectively. [18] ROS synergistically increases the risk for getting cancer when combined with estrogen, as shown in a hamster kidney cancer model.…”

Vitamin D deficiency in minority populations

“…A growing literature (1)(2)(3) suggests that vitamin D may be associated with reduced mortality (overall (4) and hospital-associated (5) ), incidence of cancer (6)(7)(8)(9)(10)(11)(12)(13) , CVD (14,15) , diabetes (16) , fractures (17,18) and ageing-related functional limitations (19) , although some studies find an unclear relationship (20,21) or a harmful association with disease (22) . Randomized controlled trials are underway to examine the potential role of vitamin D in the prevention of multiple diseases, including cancer, CVD and diabetes (20,23) .…”