Article

Serum Vitamin D and Risk of Bladder Cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial

Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.32). 05/2012; 21(7):1222-5. DOI: 10.1158/1055-9965.EPI-12-0439
Source: PubMed

ABSTRACT The one previous prospective study of vitamin D status and risk of urinary bladder cancer found that male smokers with low serum 25-hydroxy-vitamin D [25(OH)D] were at a nearly two-fold increased risk. We conducted an analysis of serum 25(OH)D and risk of bladder cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Study and examined whether serum vitamin D binding protein (DBP) concentration confounded or modified the association.
Three hundred and seventy-five cases of bladder cancer were matched 1:1 with controls based on age (±5 years), race, sex, and date of blood collection (±30 days). Conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI) of bladder cancer by prediagnosis levels of 25(OH)D.
We found no strong or statistically significant association between serum 25(OH)D and bladder cancer risk (Q1 vs. Q4: OR, 0.84; 95% CI, 0.52-1.36; P(trend) = 0.56). Further adjustment for, or stratification by, serum DBP did not alter the findings, nor was there a main effect association between DBP and risk.
In contrast to an earlier report, we observed no association between vitamin D status and risk of bladder cancer; this difference could be due to the inclusion of women and nonsmokers in the current study population or due to the differences in the distribution of vitamin D concentrations between the two study populations.
These findings may contribute to future meta-analyses and help elucidate whether the vitamin D-bladder cancer association varies across populations.

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    ABSTRACT: Background Previous evidence suggests that 25-hydroxyvitamin D(3) [25(OH)D(3)] protects against several cancers. However, little is known regarding urothelial bladder cancer (UBC). We analyzed the association between plasma 25(OH)D(3) and overall risk of UBC, as well as according to stage and FGFR3 molecular subphenotypes.Methods Plasma concentrations of 25(OH)D(3) in 1125 cases with UBC and 1028 control subjects were determined by a chemiluminescence immunoassay. FGFR3 mutational status and expression in tumor tissue were assessed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression adjusting for potential confounders. Analyses were further stratified by tumor invasiveness and grade, FGFR3 expression, and smoking status. Cell proliferation was measured in human UBC cell lines cultured with 1α,25-dihydroxyvitamin D(3). ResultsA statistically significantly increased risk of UBC was observed among subjects presenting the lowest concentrations of 25(OH)D(3) (OR(adj) = 1.83; 95% CI = 1.19 to 2.82; P = .006), showing a dose-response effect (P (trend) = .004). The association was stronger for patients with muscle-invasive tumors, especially among low-FGFR3 expressers (OR(adj) = 5.94; 95% CI = 1.72 to 20.45; P = .005). The biological plausibility of these associations is supported by the fact that, in vitro, 1α,25-dihydroxyvitamin D(3) upregulates FGFR3 expression in UBC cell lines with low levels of wild-type FGFR3.Conclusion These findings support a role of vitamin D in the pathogenesis of UBC and show that 25(OH)D(3) levels are associated with FGFR3 expression in the tumor. Because FGFR3 mutation and overexpression are markers of better outcome, our findings suggest that individuals with low levels of plasma 25(OH)D(3) may be at high risk of more aggressive forms of UBC.
    CancerSpectrum Knowledge Environment 12/2012; 104(24):1897-1904. DOI:10.1093/jnci/djs444 · 15.16 Impact Factor
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Alison M Mondul