A Collaborative Analysis of Individual Participant Data from 19 Prospective Studies Assesses Circulating Vitamin D and Prostate Cancer Risk

Abstract

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between pre-diagnostic concentrations of 25-hydroxyvitamin D (25(OH)D) and 1,25(OH)2D and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. Odds ratios (OR) for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest versus lowest study-specific fifth was 1.22, 95% CI 1.13-1.31; P trend<0.001). However, this association varied by disease aggressiveness (Pheterogeneity=0.014); higher circulating 25(OH)D was associated with a higher risk of non-aggressive disease (OR per 80 percentile increase=1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of non-aggressive prostate cancer may be influenced by detection bias.

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

“…Bone-and joint-related biomarkers Higher circulating vitamin D concentrations were associated with a higher risk of prostate cancer diagnosis in the current study, which is consistent with a previous individual participant meta-analysis of prospective studies; 29 however, this association was not significant after excluding the first 4 years of follow-up. This finding may reflect detection bias; health-conscious men may have a higher dietary intake of vitamin D and/or vitamin D supplementation and higher sun exposure, and these men may be more likely to have a prostate specific antigen (PSA) test or to seek medical attention with early symptoms.…”

Molecular evidence of IGFBP-3 dependent and independent VD3 action and its nonlinear response on IGFBP-3 induction in prostate cancer cells

“…Consistent with such finding, for example, an increase in colon cancer incidence with lower vitamin D dietary habits has been reported [10,11]. However, suppressive effect on prostate cancer is still under discussion [12,13].…”

“…Although epidemiological studies have indicated the benefit of using VD3 in the preventing tumorigenesis in multiple cancer types, it benefit in prostate cancer prevention is unclear [9,[12][13][14]. Meanwhile, the efficacy of VD3 in prostate cancer chemotherapy has been expected, but its efficacy as a single agent has not been determined and its use as a concomitant drug with anticancer drugs remains under discussion [20].…”

“…Although the impact of vitamin D as a single agent on prostate cancer has been investigated, its significance remains under discussion [12,13]. Meanwhile, the synergistic or additive effects of vitamin D and its derivatives, with anticancer drugs, on prostate cancer have been clinically studied, and encouraging results have been reported [17,18].…”

The Association of a Novel Identified VDR SNP With Prostate Cancer in African American Men

“…Vitamin D (VD) has been reported as an important candidate implicated in the risk of prostate cancer (1)(2)(3)(4)(5). Although the exact mechanism of action is uncertain, various investigators have shown that serum 1,25-Dihydroxyvitamin D [1,25(OH)2 VD] levels can affect tumor cell proliferation and differentiation (6)(7)(8)(9)(10)(11)(12).…”