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Genetic variation in the TP53 pathway and bladder cancer risk: a comprehensive analysis

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dc.contributor.author Pineda, Silvia
dc.contributor.author Milne, Roger L.
dc.contributor.author Calle, M. Luz
dc.contributor.author Rothman, Nathaniel
dc.contributor.author López De Maturana, Evangelina
dc.contributor.author Herranz, Jesús
dc.contributor.author Kogevinas, Manolis
dc.contributor.author Chanock, Stephen J.
dc.contributor.author Tardón, Adonina
dc.contributor.author Márquez, Mirari
dc.contributor.author Guey, Lin T.
dc.contributor.author García Closas, Montserrat
dc.contributor.author Lloreta Trull, Josep, 1958-
dc.contributor.author Baum, Erin
dc.contributor.author González Neira, Anna
dc.contributor.author Carrato, Alfredo
dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-
dc.contributor.author Silverman, Debra T.
dc.contributor.author Real, Francisco X.
dc.contributor.author Malats i Riera, Núria
dc.date.accessioned 2015-05-22T07:45:34Z
dc.date.available 2015-05-22T07:45:34Z
dc.date.issued 2014
dc.identifier.citation Pineda S, Milne RL, Calle ML, Rothman N, López De Maturana E, Herranz J et al. Genetic variation in the TP53 pathway and bladder cancer risk: a comprehensive analysis. PLoS ONE. 2014;9(5):e89952. DOI: 10.1371/journal.pone.0089952
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/23617
dc.description.abstract Introduction: Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk. Material and Methods: We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998–2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously. Results: Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value≤0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value≥0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05–1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation. Discussion: We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies.
dc.description.sponsorship This work was supported by the Fondo de Investigación Sanitaria, Spain (grant numbers 00/0745, PI051436, PI061614, G03/174); Red Temá tica de Investigación Cooperativa en Cáncer (grant number RD06/0020-RTICC), Spain; Marató TV3 (grant number 050830); European Commission (grant numbers EU-FP7-HEALTH-F2-2008-201663-UROMOL; US National Institutes of Health (grant number USA-NIH-RO1-CA089715); and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute at the National Institutes of Health, USA; Consolider ONCOBIO (Ministerio de Economía y Competitividad, Madrid, Spain).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS ONE. 2014;9(5):e89952
dc.rights © 2014 Pineda et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.subject.other Genètica
dc.subject.other Polimorfisme genètic
dc.title Genetic variation in the TP53 pathway and bladder cancer risk: a comprehensive analysis
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0089952
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/201663
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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