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Título:
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Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis
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Autor/a:
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Pineda, S.; Milne, R.L.; Calle, M. Luz; Rothman, Nathaniel; López de Maturana, Evangelina; Herranz, J.; Kogevinas, Manolis; Chanock, Stephen; Tardón, Adonina; Márquez, M.; Guey, Lin T.; García-Closas, Montserrat; Lloreta, Josep; Baum, E.; González-Neira, Anna; Carrato, Alfredo; Navarro, Arcadi; Silverman, Debra T.; Real, Francisco X.; Malats i Riera, Núria
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Otros autores:
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Universitat de Vic. Escola Politècnica Superior; Universitat de Vic. Grup de Recerca en Bioinformàtica i Estadística Mèdica |
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Notas:
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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.
This work was supported by the Fondo de Investigacion Sanitaria, Spain (grant numbers 00/0745, PI051436, PI061614, G03/174); Red Tematica de Investigacion Cooperativa en Cancer (grant number RD06/0020-RTICC), Spain; Marato 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 Economia y Competitividad, Madrid, Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
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Materia(s):
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-Càncer -- Aspectes genètics |
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Derechos:
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Aquest document està subjecte a aquesta llicència Creative Commons
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
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Tipo de documento:
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Artículo
info:eu-repo/publishedVersion |
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Editor:
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Public Library of Science
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