Prediagnostic Serum 25-Hydroxyvitamin D and Mortality Among Bladder Cancer Patients in the Janus Serum Bank Cohort

Abstract

Purpose Circulating 25-hydroxyvitamin D (25(OH)D) is inversely associated with overall cancer mortality and selected cancers, while for urothelial bladder cancer (BC) this relationship is unclear. We aimed to examine the association between 25(OH)D and BC mortality. Materials and Methods We used prediagnostic serum from 378 BC cases within the population-based Janus Cohort. Cox regression models estimated hazard ratios (HRs), with 95% confidence intervals (CIs), for the association between 25(OH)D and BC-specific and all-cause mortality. Restricted cubic splines were assessed to examine non-linear risk associations. Analyses were stratified by tumor invasiveness (non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC)). Additionally, the association between 25(OH)D and all-cause mortality was assessed for 378 cancer-free matched controls. Results 25(OH)D deficiency (<50 nmol/L) was associated with higher BC-specific mortality (HR 1.87, 95% CI 1.10–3.20), when compared with insufficient levels (50–74 nmol/L). Stratification by tumor invasiveness revealed that this result was evident for NMIBC only, both with respect to BC-specific mortality (HR 2.84, 95% CI 1.14–7.12) and all-cause mortality (HR 1.97, 95% CI 1.06–3.65). No association between 25(OH)D levels and all-cause mortality was found in cancer-free controls. Conclusion 25(OH)D deficiency (<50 nmol/L) prior to a BC diagnosis was associated with increased risk of BC-specific mortality, when compared to insufficient levels (50–74 nmol/L). The results were evident among NMIBC patients only, suggesting a more critical role of vitamin D deficiency in an early stage of the disease.