Vitamin D and Prostate Cancer

Krishnan, Aruna V.; Feldman, David

doi:10.1016/b978-0-12-381978-9.10086-1

Cited by 5 publications

(5 citation statements)

References 334 publications

(398 reference statements)

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“…Anti-tumor effects of vitamin D in animal models for cancers are well-documented [ 45 ]. Detailed discussions about vitamin D actions in cancers of the breast [ 46 ], prostate [ 47 ], colorectum [ 48 ], hematological malignancies [ 49 ] and other cancers [ 50 ], have established the plausibility of a causal role between vitamin D and cancer. However, as emphasized by Jacobs et al [ 51 ], it has been challenging to reconcile the results from laboratory studies, demonstrating the biological mechanisms of the active hormone form of vitamin D (1,25(OH) 2 D), and the observational studies, using levels of circulating 25-OHD.…”

Section: Discussionmentioning

confidence: 99%

The Inverse Relationship between 25-Hydroxyvitamin D and Cancer Survival: Discussion of Causation

Robsahm

Schwartz

Tretli

2013

Cancers

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Cancer mortality rates vary inversely with geographic latitude and solar ultraviolet-B doses. This relationship may be due to an inhibitory role of vitamin D on cancer development. The relationship between vitamin D and cancer appears to be stronger for studies of cancer mortality than incidence. Because cancer mortality reflects both cancer incidence and survival, the difference may be due to effects of vitamin D on cancer survival. Here we review analytic epidemiologic studies investigating the relation between vitamin D, measured by circulating levels of 25-hydroxyvitamin D (25-OHD), and cancer survival. A relationship between low 25-OHD levels and poor survival is shown by most of the reviewed studies. This relationship is likely to be causal when viewed in light of most criteria for assessing causality (temporality, strength, exposure-response, biological plausibility and consistency). A serum level of 25-OHD around 50 nmol/L appears to be a threshold level. Conversely, there are several mechanisms whereby cancer could lower serum levels of 25-OHD. The severity of disease at the time of diagnosis and time of serum sampling are key factors to clarify the temporal aspect of these relationships. Evidence that vitamin D supplementation could retard the disease process or prolong survival time would be key evidence, but is difficult to generate. However, recent clinical trial results in prostate cancer support a role for vitamin D in this regard.

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Section: Discussionmentioning

confidence: 99%

The Inverse Relationship between 25-Hydroxyvitamin D and Cancer Survival: Discussion of Causation

Robsahm

Schwartz

Tretli

2013

Cancers

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“…For example the absence of intact VDR or loss of function mutations in the VDR would decrease or eliminate responses to any levels of calcitriol. Many factors regulate the concentration of VDR in target cells altering the magnitude of the response to calcitriol (Krishnan and Feldman, 1997). A recent study examining the expression of VDR protein by immunohistochemistry in 841 patients with PCa concluded that high expression of VDR in prostate tumors is associated with a reduced risk of lethal cancer (Hendrickson et al, 2011) suggesting a role for the VDR pathway in its ability to inhibit PCa progression that is dependent upon VDR content and not just 25(OH)D blood levels.…”

Section: Vitamin D Actionsmentioning

confidence: 99%

“…This action leads to an increase in calcitriol half-life in DU 145 cells and thereby allows a substantial calcitriol anti-proliferative effect (Ly et al, 1999). In many target cells, including PCa cells (Swami et al, 2005), calcitriol causes homologous up-regulation of VDR levels (Costa et al, 1985; Krishnan and Feldman, 1997). Prolongation of calcitriol half-life (due to the inhibition of 24-hydroxylase by liarozole) also leads to an enhanced up-regulation of VDR in DU 145 cells making them more responsive to calcitriol (Ly et al, 1999).…”

Section: Combination Therapy Of Calcitriol With Other Drugsmentioning

confidence: 99%

“…Trump and colleagues have added dexamethasone to a combination of ketoconazole and calcitriol in experimental models of PCa (Muindi et al, 2010). The rationale for this approach is that dexamethasone serves to minimize calcitriol-induced hypercalcemia due possibly to a down-regulation of VDR in the intestine (Hidalgo et al, 2010; Krishnan and Feldman, 1997) as well as to serve as a glucocorticoid replacement for ketoconazole inhibition of adrenal steroidogenesis. Currently more specific inhibitors of 24-hydroxylase, both azoles and cholecalciferol analogs, are being developed.…”

Section: Combination Therapy Of Calcitriol With Other Drugsmentioning

confidence: 99%

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Vitamin D metabolism and action in the prostate: Implications for health and disease

Swami

Krishnan

Feldman

2011

Molecular and Cellular Endocrinology

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Prostate cancer (PCa) is the second most common cancer in men worldwide. Epidemiological, molecular, and cellular studies have implicated vitamin D deficiency as a risk factor for the development and/or progression of PCa. Studies using cell culture systems and animal models suggest that vitamin D acts to reduce the growth of PCa through regulation of cellular proliferation and differentiation. However, although pre-clinical studies provide a strong indication for anti-cancer activity, proof of therapeutic benefits in men is still lacking. The anti-proliferative and pro-differentiating properties of vitamin D have been attributed to calcitriol [1,25(OH)2D3], the hormonally active form of vitamin D, acting through the vitamin D receptor (VDR). Metabolism of vitamin D in target tissues is mediated by two key enzymes: 1α-hydroxylase (CYP27B1), which catalyzes the synthesis of calcitriol from 25(OH)D and 24-hydroxylase (CYP24), which catalyzes the initial step in the conversion of calcitriol to less active metabolites. Many factors affect the balance of calcitriol synthesis and catabolism and several maneuvers, like combination therapy of calcitriol with other drugs, have been explored to treat PCa and reduce its risk. The current paper is an overview addressing some of the key factors that influence the biological actions of vitamin D and its metabolites in the treatment and/or prevention of PCa.

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“…Several mechanisms of vitamin D-mediated anticancer action have been identified [19]. Vitamin D suppresses the expression of cyclo-oxygenase-II, the key enzyme for the synthesis of prostaglandins, mediators of inflammation and thought to be important for cancer progression [20]; cyclo-oxygenase-II expression in biopsy cores and prostate cancer surgical specimen is an independent predictor of recurrence [21].…”

mentioning

confidence: 99%

Systems Analysis of the Prostate Transcriptome in African–American Men Compared with European–American Men

et al. 2016

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Vitamin D and Prostate Cancer

Cited by 5 publications

References 334 publications

The Inverse Relationship between 25-Hydroxyvitamin D and Cancer Survival: Discussion of Causation

The Inverse Relationship between 25-Hydroxyvitamin D and Cancer Survival: Discussion of Causation

Vitamin D metabolism and action in the prostate: Implications for health and disease

Systems Analysis of the Prostate Transcriptome in African–American Men Compared with European–American Men

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