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

Simple item page
dc.contributor.authorPineda Sanjuan, Silvia
dc.contributor.authorMilne, Roger
dc.contributor.authorCalle, M Luz
dc.contributor.authorRothman, Nathaniel
dc.contributor.authorLópez de Maturana, Evangelina
dc.contributor.authorHerranz, Jesús
dc.contributor.authorKogevinas, Manolis
dc.contributor.authorChanock, Stephen
dc.contributor.authorTardón, Adonina
dc.contributor.authorMárquez, Mirari
dc.contributor.authorGuey, Lin T
dc.contributor.authorGarcía-Closas, Montserrat
dc.contributor.authorLloreta, Josep
dc.contributor.authorBaum, Erin
dc.contributor.authorGonzález-Neira, Anna
dc.contributor.authorCarrato, Alfredo
dc.contributor.authorNavarro, Arcadi
dc.contributor.authorSilverman, Debra
dc.contributor.authorReal, Francisco
dc.contributor.authorMaltas, Núria
dc.contributor.editorChenette, Emily
dc.date.accessioned2024-01-31T12:25:07Z
dc.date.available2024-01-31T12:25:07Z
dc.date.issued2014
dc.description.abstractIntroduction: 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.departmentDepto. de Estadística y Ciencia de los Datos
dc.description.facultyFac. de Estudios Estadísticos
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Sanidad (España)
dc.description.sponsorshipMarató TV3
dc.description.sponsorshipEuropean Commission
dc.description.sponsorshipUS National Institute of Health
dc.description.sponsorshipMinisterio de Economía y Competitividad (España)
dc.description.statuspub
dc.identifier.citationPineda S, Milne RL, Calle ML, Rothman N, Lo´ pez de Maturana E, et al. (2014) Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis. PLoS ONE 9(5): e89952.
dc.identifier.doi10.1371/journal.pone.0089952
dc.identifier.issn1932-6203
dc.identifier.officialurlhttps://doi.org/10.1371/journal.pone.0089952
dc.identifier.relatedurlhttps://journals.plos.org/plosone/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/97109
dc.issue.number5
dc.journal.titlePlos One
dc.language.isoeng
dc.page.final8
dc.page.initial1
dc.publisherPublic Library of Science. San Francisco, CA.
dc.relation.projectID00/0745
dc.relation.projectIDPI051436
dc.relation.projectIDPI061614
dc.relation.projectIDG03/174
dc.relation.projectIDRD06/0020-RTICC
dc.relation.projectID050830
dc.relation.projectIDEU-FP7- HEALTH-F2-2008-201663-UROMOL
dc.relation.projectIDUSA-NIH-RO1-CA089715
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu575
dc.subject.ucmGenética
dc.subject.unesco2409 Genética
dc.titleGenetic variation in the TP53 pathway and bladder cancer risk. a comprehensive analysis
dc.typejournal article
dc.type.hasVersionAM
dc.volume.number9
dspace.entity.typePublication
relation.isAuthorOfPublication9ff02bb9-3623-452e-ad72-8bb19687ec4e
relation.isAuthorOfPublication.latestForDiscovery9ff02bb9-3623-452e-ad72-8bb19687ec4e
Download
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Genetic_varation_in_the_TP53.pdf
Size:
340.31 KB
Format:
Adobe Portable Document Format
downoload Download
Collections
Artículos