Prognostic relevance of urinary bladder cancer susceptibility loci.

In the last few years, susceptibility loci have been identified for urinary bladder cancer (UBC) through candidate-gene and genome-wide association studies. Prognostic relevance of most of these loci is yet unknown. In this study, we used data of the Nijmegen Bladder Cancer Study (NBCS) to perform a...

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Autores principales:	Anne J Grotenhuis, Aleksandra M Dudek, Gerald W Verhaegh, J Alfred Witjes, Katja K Aben, Saskia L van der Marel, Sita H Vermeulen, Lambertus A Kiemeney
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ed9e22312aed4b26910fb7d7392251ac
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spelling	oai:doaj.org-article:ed9e22312aed4b26910fb7d7392251ac2021-11-18T08:31:10ZPrognostic relevance of urinary bladder cancer susceptibility loci.1932-620310.1371/journal.pone.0089164https://doaj.org/article/ed9e22312aed4b26910fb7d7392251ac2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586564/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In the last few years, susceptibility loci have been identified for urinary bladder cancer (UBC) through candidate-gene and genome-wide association studies. Prognostic relevance of most of these loci is yet unknown. In this study, we used data of the Nijmegen Bladder Cancer Study (NBCS) to perform a comprehensive evaluation of the prognostic relevance of all confirmed UBC susceptibility loci. Detailed clinical data concerning diagnosis, stage, treatment, and disease course of a population-based series of 1,602 UBC patients were collected retrospectively based on a medical file survey. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed, and log-rank tests calculated, to evaluate the association between 12 confirmed UBC susceptibility variants and recurrence and progression in non-muscle invasive bladder cancer (NMIBC) patients. Among muscle-invasive or metastatic bladder cancer (MIBC) patients, association of these variants with overall survival was tested. Subgroup analyses by tumor aggressiveness and smoking status were performed in NMIBC patients. In the overall NMIBC group (n = 1,269), a statistically significant association between rs9642880 at 8q24 and risk of progression was observed (GT vs. TT: HR = 1.08 (95% CI: 0.76-1.54), GG vs. TT: HR = 1.81 (95% CI: 1.23-2.66), P for trend = 2.6 × 10(-3)). In subgroup analyses, several other variants showed suggestive, though non-significant, prognostic relevance for recurrence and progression in NMIBC and survival in MIBC. This study provides suggestive evidence that genetic loci involved in UBC etiology may influence disease prognosis. Elucidation of the causal variant(s) could further our understanding of the mechanism of disease, could point to new therapeutic targets, and might aid in improvement of prognostic tools.Anne J GrotenhuisAleksandra M DudekGerald W VerhaeghJ Alfred WitjesKatja K AbenSaskia L van der MarelSita H VermeulenLambertus A KiemeneyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89164 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anne J Grotenhuis Aleksandra M Dudek Gerald W Verhaegh J Alfred Witjes Katja K Aben Saskia L van der Marel Sita H Vermeulen Lambertus A Kiemeney Prognostic relevance of urinary bladder cancer susceptibility loci.
description	In the last few years, susceptibility loci have been identified for urinary bladder cancer (UBC) through candidate-gene and genome-wide association studies. Prognostic relevance of most of these loci is yet unknown. In this study, we used data of the Nijmegen Bladder Cancer Study (NBCS) to perform a comprehensive evaluation of the prognostic relevance of all confirmed UBC susceptibility loci. Detailed clinical data concerning diagnosis, stage, treatment, and disease course of a population-based series of 1,602 UBC patients were collected retrospectively based on a medical file survey. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed, and log-rank tests calculated, to evaluate the association between 12 confirmed UBC susceptibility variants and recurrence and progression in non-muscle invasive bladder cancer (NMIBC) patients. Among muscle-invasive or metastatic bladder cancer (MIBC) patients, association of these variants with overall survival was tested. Subgroup analyses by tumor aggressiveness and smoking status were performed in NMIBC patients. In the overall NMIBC group (n = 1,269), a statistically significant association between rs9642880 at 8q24 and risk of progression was observed (GT vs. TT: HR = 1.08 (95% CI: 0.76-1.54), GG vs. TT: HR = 1.81 (95% CI: 1.23-2.66), P for trend = 2.6 × 10(-3)). In subgroup analyses, several other variants showed suggestive, though non-significant, prognostic relevance for recurrence and progression in NMIBC and survival in MIBC. This study provides suggestive evidence that genetic loci involved in UBC etiology may influence disease prognosis. Elucidation of the causal variant(s) could further our understanding of the mechanism of disease, could point to new therapeutic targets, and might aid in improvement of prognostic tools.
format	article
author	Anne J Grotenhuis Aleksandra M Dudek Gerald W Verhaegh J Alfred Witjes Katja K Aben Saskia L van der Marel Sita H Vermeulen Lambertus A Kiemeney
author_facet	Anne J Grotenhuis Aleksandra M Dudek Gerald W Verhaegh J Alfred Witjes Katja K Aben Saskia L van der Marel Sita H Vermeulen Lambertus A Kiemeney
author_sort	Anne J Grotenhuis
title	Prognostic relevance of urinary bladder cancer susceptibility loci.
title_short	Prognostic relevance of urinary bladder cancer susceptibility loci.
title_full	Prognostic relevance of urinary bladder cancer susceptibility loci.
title_fullStr	Prognostic relevance of urinary bladder cancer susceptibility loci.
title_full_unstemmed	Prognostic relevance of urinary bladder cancer susceptibility loci.
title_sort	prognostic relevance of urinary bladder cancer susceptibility loci.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ed9e22312aed4b26910fb7d7392251ac
work_keys_str_mv	AT annejgrotenhuis prognosticrelevanceofurinarybladdercancersusceptibilityloci AT aleksandramdudek prognosticrelevanceofurinarybladdercancersusceptibilityloci AT geraldwverhaegh prognosticrelevanceofurinarybladdercancersusceptibilityloci AT jalfredwitjes prognosticrelevanceofurinarybladdercancersusceptibilityloci AT katjakaben prognosticrelevanceofurinarybladdercancersusceptibilityloci AT saskialvandermarel prognosticrelevanceofurinarybladdercancersusceptibilityloci AT sitahvermeulen prognosticrelevanceofurinarybladdercancersusceptibilityloci AT lambertusakiemeney prognosticrelevanceofurinarybladdercancersusceptibilityloci
_version_	1718421717730197504

Prognostic relevance of urinary bladder cancer susceptibility loci.

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