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

Pineda, Silvia; Milne, Roger L.; Calle, M. Luz; Rothman, Nathaniel; López De Maturana, Evangelina; Herranz, Jesús; Kogevinas, Manolis; Chanock, Stephen J.; Tardón, Adonina; Márquez, Mirari; Guey, Lin T.; García Closas, Montserrat; Lloreta, Josep, 1958-; Baum, Erin; González Neira, Anna; Carrato, Alfredo; Navarro i Cuartiellas, Arcadi, 1969-; Silverman, Debra T.; Real, Francisco X.; Malats i Riera, Núria

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

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dc.contributor.author Pineda, Silviaca
dc.contributor.author Milne, Roger L.ca
dc.contributor.author Calle, M. Luzca
dc.contributor.author Rothman, Nathanielca
dc.contributor.author López De Maturana, Evangelinaca
dc.contributor.author Herranz, Jesúsca
dc.contributor.author Kogevinas, Manolisca
dc.contributor.author Chanock, Stephen J.ca
dc.contributor.author Tardón, Adoninaca
dc.contributor.author Márquez, Mirarica
dc.contributor.author Guey, Lin T.ca
dc.contributor.author García Closas, Montserratca
dc.contributor.author Lloreta, Josep, 1958-ca
dc.contributor.author Baum, Erinca
dc.contributor.author González Neira, Annaca
dc.contributor.author Carrato, Alfredoca
dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-ca
dc.contributor.author Silverman, Debra T.ca
dc.contributor.author Real, Francisco X.ca
dc.contributor.author Malats i Riera, Núriaca
dc.date.accessioned 2015-05-22T07:45:34Z
dc.date.available 2015-05-22T07:45:34Z
dc.date.issued 2014ca
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.en
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).en
dc.format.mimetype application/pdfca
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.0089952ca
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0089952
dc.identifier.issn 1932-6203ca
dc.identifier.uri http://hdl.handle.net/10230/23617
dc.language.iso engca
dc.publisher Public Library of Science (PLoS)ca
dc.relation.ispartof PLoS ONE. 2014;9(5):e89952
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/201663ca
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.en
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.other Genèticaca
dc.subject.other Polimorfisme genèticca
dc.title Genetic variation in the TP53 pathway and bladder cancer risk: a comprehensive analysisen
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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