Dataset Information

Plasma 25-hydroxyvitamin D(3) and bladder cancer risk according to tumor stage and FGFR3 status: a mechanism-based epidemiological study.

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).

Results

A 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.

SUBMITTER: Amaral AF

PROVIDER: S-EPMC3525815 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Publications

Plasma 25-hydroxyvitamin D(3) and bladder cancer risk according to tumor stage and FGFR3 status: a mechanism-based epidemiological study.

Amaral André F S AF Méndez-Pertuz Marinela M Muñoz Alberto A Silverman Debra T DT Allory Yves Y Kogevinas Manolis M Lloreta Josep J Rothman Nathaniel N Carrato Alfredo A Rivas del Fresno Manuel M Real Francisco X FX Malats Núria N

Journal of the National Cancer Institute 20121029 24

<h4>Background</h4>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.<h4>Methods</h4>Plasma concentrations of 25(OH)D(3) in 1125 cases with UBC and 1028 control subjects were determined by a chemiluminescence immunoassay. FGFR3 mutationa ...[more]

PMID: 23108201

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Project description:Laboratory studies suggest that vitamin D may inhibit pancreatic cancer cell growth. However, epidemiologic studies of vitamin D and pancreatic cancer risk have been conflicting.To determine whether prediagnostic levels of plasma 25-hydroxyvitamin D (25[OH]D; IDS Inc.; enzyme immunoassay) were associated with risk of pancreatic cancer, we conducted a pooled analysis of nested case-control studies with 451 cases and 1,167 controls from five cohorts through 2008. Median follow-up among controls was 14.1 years in Health Professionals Follow-Up Study (HPFS), 18.3 years in Nurses' Health Study (NHS), 25.3 years in Physicians' Health Study (PHS), 12.2 years in Women's Health Initiative-Observational Study (WHI), and 14.4 years in Women's Health Study (WHS). Logistic regression was used to compare the odds of pancreatic cancer by plasma level of 25(OH)D.Mean plasma 25(OH)D was lower in cases versus controls (61.3 vs. 64.5 nmol/L, P = 0.005). In logistic regression models, plasma 25(OH)D was inversely associated with odds of pancreatic cancer. Participants in quintiles two through five had multivariable-adjusted ORs (95% confidence intervals) of 0.79 (0.56-1.10), 0.75 (0.53-1.06), 0.68 (0.48-0.97), and 0.67 (0.46-0.97; P(trend) = 0.03), respectively, compared with the bottom quintile. Compared with those with insufficient levels [25[OH]D, <50 nmol/L], ORs were 0.75 (0.58-0.98) for subjects with relative insufficiency [25[OH]D, 50 to <75 nmol/L] and 0.71 (0.52-0.97) for those with sufficient levels [25[OH]D, ? 75 nmol/L]. No increased risk was noted in subjects with 25(OH)D ?100 nmol/L, as suggested in a prior study. In subgroup analyses, ORs for the top versus bottom quartile of 25(OH)D were 0.72 (0.48-1.08) for women, 0.73 (0.40-1.31) for men, and 0.73 (0.51-1.03) for Whites.Among participants in five large prospective cohorts, higher plasma levels of 25(OH)D were associated with a lower risk for pancreatic cancer.Low circulating 25(OH)D may predispose individuals to the development of pancreatic cancer.

Dataset Information

Plasma 25-hydroxyvitamin D(3) and bladder cancer risk according to tumor stage and FGFR3 status: a mechanism-based epidemiological study.

Background

Methods

Results

Conclusion

Publications

Plasma 25-hydroxyvitamin D(3) and bladder cancer risk according to tumor stage and FGFR3 status: a mechanism-based epidemiological study.

Similar Datasets

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