Vitamin D Deficiency at Diagnosis Increases All-Cause and Prostate Cancer-specific Mortality in Jamaican Men

Abstract

Background 25 hydroxyvitamin D [25(OH)D] and serum calcium have been associated with incident prostate cancer (PCa). However, there is limited data on whether these metabolites predict survival in men of African descent, a population disproportionately affected by PCa. We studied the relationship of 25(OH)D at PCa diagnosis with all-cause and cancer-specific mortality among Jamaican men and examined whether serum calcium modified any associations. Methods Serum 25(OH)D from 152 Jamaican men with incident PCa within the Prostate Cancer Risk Evaluation (PROSCARE) study were re-evaluated approximately 11 years after enrollment. 25(OH)D analyses were stratified using the using Holick criteria. PCa-specific and all-cause mortality were examined in Kaplan–Meier survival curves and Cox regression models adjusted for age, body mass index (BMI), smoking and Gleason score. Restricted cubic splines evaluated nonlinear associations. Serum calcium was assessed as an effect modifier of the association between 25(OH)D and mortality. Results Of cases with available 25(OH)D, 64 men with PCa survived, 38 deaths were PCa specific and 36 died of other causes. At baseline, 9.9% of cases were vitamin D deficient and 61.2% were vitamin D sufficient. Compared to 25(OH)D sufficient men, those with 25(OH)D <20.0 ng/mL concentrations were associated with higher PCa-specific mortality (adjusted HR, 4.95; 95% CI, 1.68, 14.63, P = .004) and all-cause mortality (adjusted HR, 2.40; 95%CI, 1.33, 4. 32, P = .003). Serum calcium was not associated with survival and did not modify any associations with 25(OH)D. Conclusions 25(OH)D deficiency at PCa diagnosis predicted decreased survival for overall and PCa-specific cancer in Caribbean men of African ancestry.

Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer

“…Elements such as VD itself and its associated enzymes, including VDR, have been shown to influence PCa proliferation, invasion, and resistance to treatment [ 7 – 10 ]. Retrospective clinical studies have underscored the significant correlation between abnormal serum vitamin levels and PCa prognosis [ 11 , 12 ]. Notably, a single-cell sequencing investigation conducted in genetically engineered Pten (i)pe−/− mice revealed that VD analogs can induce apoptosis in senescent prostatic intraepithelial neoplasia and diminish the infiltration of myeloid-derived suppressor cells within the prostate [ 13 ].…”

Possible non-linear relation between prostate specific antigen and vitamin D: a machine learning study based on cross-section data

“…The potential role of 25(OH)D compounds in cancer's etiology and treatment has been explored since the early 1970s. Hamster models exhibited cancer development inhibition with 25(OH)D compound treatment, and human cancer cells showed the presence of the 25(OH)D receptor (VDR), associated with in vitro growth arrest [7][8][9][10].…”