Inflammatory-Related Genetic Variants in Non-Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment.
Cancer Epidemiol Biomarkers Prev
; 25(7): 1144-50, 2016 07.
Article
em En
| MEDLINE
| ID: mdl-27197286
ABSTRACT
BACKGROUND:
Increasing evidence points to the role of tumor immunologic environment on urothelial bladder cancer prognosis. This effect might be partly dependent on the host genetic context. We evaluated the association of SNPs in inflammation-related genes with non-muscle-invasive bladder cancer (NMIBC) risk-of-recurrence and risk-of-progression.METHODS:
We considered 822 NMIBC included in the SBC/EPICURO Study followed-up >10 years. We selected 1,679 SNPs belonging to 251 inflammatory genes. The association of SNPs with risk-of-recurrence and risk-of-progression was assessed using Cox regression single-marker (SMM) and multimarker methods (MMM) Bayes A and Bayesian LASSO. Discriminative abilities of the models were calculated using the c index and validated with bootstrap cross-validation procedures.RESULTS:
While no SNP was found to be associated with risk-of-recurrence using SMM, three SNPs in TNIP1, CD5, and JAK3 showed very strong association with posterior probabilities >90% using MMM. Regarding risk-of-progression, one SNP in CD3G was significantly associated using SMM (HR, 2.69; P = 1.55 × 10(-5)) and two SNPs in MASP1 and AIRE, showed a posterior probability ≥80% with MMM. Validated discriminative abilities of the models without and with the SNPs were 58.4% versus 60.5% and 72.1% versus 72.8% for risk-of-recurrence and risk-of-progression, respectively.CONCLUSIONS:
Using innovative analytic approaches, we demonstrated that SNPs in inflammatory-related genes were associated with NMIBC prognosis and that they improve the discriminative ability of prognostic clinical models for NMIBC. IMPACT This study provides proof of concept for the joint effect of genetic variants in improving the discriminative ability of clinical prognostic models. The approach may be extended to other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1144-50. ©2016 AACR.
Texto completo:
1
Temas:
ECOS
/
Aspectos_gerais
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
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Carcinoma de Células de Transição
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Biomarcadores Tumorais
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Epidemiol Biomarkers Prev
Assunto da revista:
BIOQUIMICA
/
EPIDEMIOLOGIA
/
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
França