Vitamin D and Vitamin D-binding protein and risk of bladder cancer: A nested case-control study in the Norwegian Janus Serum Bank Cohort.
Adult
Body Mass Index
Case-Control Studies
Cohort Studies
Confidence Intervals
Educational Status
Exercise
Female
Humans
Male
Middle Aged
Norway
Proportional Hazards Models
Risk Assessment
Smoking
Time Factors
Urinary Bladder Neoplasms
/ blood
Vitamin D
/ analogs & derivatives
Vitamin D-Binding Protein
/ blood
bladder cancer risk
cancer risk
case-control study
vitamin D
vitamin-binding protein
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
05
04
2021
received:
16
11
2020
accepted:
07
04
2021
pubmed:
4
6
2021
medline:
25
12
2021
entrez:
3
6
2021
Statut:
ppublish
Résumé
High circulating levels of vitamin D (25(OH)D) are suggested to reduce the risk of urinary bladder cancer (BC), but the evidence is weak, and several studies lack sufficient adjustment for potential confounders (e.g., smoking, body mass index (BMI), and physical activity). Moreover, few studies have investigated the role of vitamin D-binding protein (DBP) in this context. We conducted a matched nested case-control study including 378 cases and 378 controls within the Norwegian population-based Janus cohort, using serum collected 5-41 years prior to diagnosis, to study 25(OH)D and BC risk, by taking circulating DBP into account. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), for 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, an estimate of unbound (free) 25(OH)D levels. We adjusted for smoking (status and pack-years), BMI, physical activity, education and (mutually) for 25(OH)D and DBP. Restricted cubic splines were employed to examine nonlinear associations. High optimal levels of circulating 25(OH)D (≥100 nmol/L) (HR 0.35, 95% CI 0.19-0.64) were associated with decreased BC risk, when compared with insufficient concentrations (50-74 nmol/L). This association was less pronounced for optimal levels (75-99 nmol/L) (HR = 0.69, 95% CI 0.47-1.01). Moreover, estimated free 25(OH)D, was associated with decreased BC risk for molar ratio 17-21 (HR 0.66, 95% CI 0.44-0.97) and ≥22 (HR 0.50, 95% CI 0.29-0.82), compared to molar ratio 11-16. The HR function for BC risk was not linear, rather reversed u-shaped, with the highest HR at 62.5 nmol/L and 13.5 molar ratio, respectively. High levels of total and estimated free 25(OH)D were associated with reduced risk of BC, compared with insufficient concentrations. DBP was not associated with BC risk. We did not observe any impact of DBP or any of the studied lifestyle factors on the association between 25(OH)D and BC.
Sections du résumé
BACKGROUND
High circulating levels of vitamin D (25(OH)D) are suggested to reduce the risk of urinary bladder cancer (BC), but the evidence is weak, and several studies lack sufficient adjustment for potential confounders (e.g., smoking, body mass index (BMI), and physical activity). Moreover, few studies have investigated the role of vitamin D-binding protein (DBP) in this context. We conducted a matched nested case-control study including 378 cases and 378 controls within the Norwegian population-based Janus cohort, using serum collected 5-41 years prior to diagnosis, to study 25(OH)D and BC risk, by taking circulating DBP into account.
METHODS
Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), for 25(OH)D, DBP, and the molar ratio of 25(OH)D:DBP, an estimate of unbound (free) 25(OH)D levels. We adjusted for smoking (status and pack-years), BMI, physical activity, education and (mutually) for 25(OH)D and DBP. Restricted cubic splines were employed to examine nonlinear associations.
RESULTS
High optimal levels of circulating 25(OH)D (≥100 nmol/L) (HR 0.35, 95% CI 0.19-0.64) were associated with decreased BC risk, when compared with insufficient concentrations (50-74 nmol/L). This association was less pronounced for optimal levels (75-99 nmol/L) (HR = 0.69, 95% CI 0.47-1.01). Moreover, estimated free 25(OH)D, was associated with decreased BC risk for molar ratio 17-21 (HR 0.66, 95% CI 0.44-0.97) and ≥22 (HR 0.50, 95% CI 0.29-0.82), compared to molar ratio 11-16. The HR function for BC risk was not linear, rather reversed u-shaped, with the highest HR at 62.5 nmol/L and 13.5 molar ratio, respectively.
CONCLUSION
High levels of total and estimated free 25(OH)D were associated with reduced risk of BC, compared with insufficient concentrations. DBP was not associated with BC risk. We did not observe any impact of DBP or any of the studied lifestyle factors on the association between 25(OH)D and BC.
Identifiants
pubmed: 34080787
doi: 10.1002/cam4.3960
pmc: PMC8209600
doi:
Substances chimiques
Vitamin D-Binding Protein
0
Vitamin D
1406-16-2
25-hydroxyvitamin D
A288AR3C9H
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4107-4116Informations de copyright
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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