Publication:
Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights

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dc.contributor.authorKoutros, Stella
dc.contributor.authorKiemeney, Lambertus A
dc.contributor.authorPal Choudhury, Parichoy
dc.contributor.authorMilne, Roger L
dc.contributor.authorLopez de Maturana, Evangelina
dc.contributor.authorYe, Yuanqing
dc.contributor.authorJoseph, Vijai
dc.contributor.authorFlorez-Vargas, Oscar
dc.contributor.authorDyrskjøt, Lars
dc.contributor.authorFigueroa, Jonine
dc.contributor.authorDutta, Diptavo
dc.contributor.authorGiles, Graham G
dc.contributor.authorHildebrandt, Michelle A T
dc.contributor.authorOffit, Kenneth
dc.contributor.authorKogevinas, Manolis
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorMcCullough, Marjorie L
dc.contributor.authorFreedman, Neal D
dc.contributor.authorAlbanes, Demetrius
dc.contributor.authorKooperberg, Charles
dc.contributor.authorCortessis, Victoria K
dc.contributor.authorKaragas, Margaret R
dc.contributor.authorJohnson, Alison
dc.contributor.authorSchwenn, Molly R
dc.contributor.authorBaris, Dalsu
dc.contributor.authorFurberg, Helena
dc.contributor.authorBajorin, Dean F
dc.contributor.authorCussenot, Olivier
dc.contributor.authorCancel-Tassin, Geraldine
dc.contributor.authorBenhamou, Simone
dc.contributor.authorKraft, Peter
dc.contributor.authorPorru, Stefano
dc.contributor.authorCarta, Angela
dc.contributor.authorBishop, Timothy
dc.contributor.authorSouthey, Melissa C
dc.contributor.authorMatullo, Giuseppe
dc.contributor.authorFletcher, Tony
dc.contributor.authorKumar, Rajiv
dc.contributor.authorTaylor, Jack A
dc.contributor.authorLamy, Philippe
dc.contributor.authorPrip, Frederik
dc.contributor.authorKalisz, Mark
dc.contributor.authorWeinstein, Stephanie J
dc.contributor.authorHengstler, Jan G
dc.contributor.authorSelinski, Silvia
dc.contributor.authorHarland, Mark
dc.contributor.authorTeo, Mark
dc.contributor.authorKiltie, Anne E
dc.contributor.authorTardón, Adonina
dc.contributor.authorSerra, Consol
dc.contributor.authorCarrato, Alfredo
dc.contributor.authorGarcía-Closas, Reina
dc.contributor.authorLloreta, Josep
dc.contributor.authorSchned, Alan
dc.contributor.authorLenz, Petra
dc.contributor.authorRiboli, Elio
dc.contributor.authorBrennan, Paul
dc.contributor.authorTjønneland, Anne
dc.contributor.authorOtto, Thomas
dc.contributor.authorOvsiannikov, Daniel
dc.contributor.authorVolkert, Frank
dc.contributor.authorVermeulen, Sita H
dc.contributor.authorAben, Katja K
dc.contributor.authorGalesloot, Tessel E
dc.contributor.authorTurman, Constance
dc.contributor.authorDe Vivo, Immaculata
dc.contributor.authorGiovannucci, Edward
dc.contributor.authorHunter, David J
dc.contributor.authorHohensee, Chancellor
dc.contributor.authorHunt, Rebecca
dc.contributor.authorPatel, Alpa V
dc.contributor.authorHuang, Wen-Yi
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorGago-Dominguez, Manuela
dc.contributor.authorAmiano, Pilar
dc.contributor.authorGolka, Klaus
dc.contributor.authorStern, Mariana C
dc.contributor.authorYan, Wusheng
dc.contributor.authorLiu, Jia
dc.contributor.authorLi, Shengchao Alfred
dc.contributor.authorKatta, Shilpa
dc.contributor.authorHutchinson, Amy
dc.contributor.authorHicks, Belynda
dc.contributor.authorWheeler, William A
dc.contributor.authorPurdue, Mark P
dc.contributor.authorMcGlynn, Katherine A
dc.contributor.authorKitahara, Cari M
dc.contributor.authorHaiman, Christopher A
dc.contributor.authorGreene, Mark H
dc.contributor.authorRafnar, Thorunn
dc.contributor.authorChatterjee, Nilanjan
dc.contributor.authorChanock, Stephen J
dc.contributor.authorWu, Xifeng
dc.contributor.authorReal, Francisco X
dc.contributor.authorSilverman, Debra T
dc.contributor.authorGarcia-Closas, Montserrat
dc.contributor.authorStefansson, Kari
dc.contributor.authorProkunina-Olsson, Ludmila
dc.contributor.authorMalats, Nuria
dc.contributor.authorRothman, Nathaniel
dc.contributor.funderNIH - National Cancer Institute (NCI) (Estados Unidos)es_ES
dc.contributor.funderRadboud University Medical Centeres_ES
dc.contributor.funderAsociación Española Contra el Cánceres_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderCanadian Institutes of Health Research (CIHR) Cancer Council Victoriaes_ES
dc.contributor.funderNational Health and Medical Research Council (Australia)es_ES
dc.date.accessioned2024-09-16T08:17:11Z
dc.date.available2024-09-16T08:17:11Z
dc.date.issued2023-07
dc.description.abstractBackground: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. Objective: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. Design, setting, and participants: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. Outcome measurements and statistical analyses: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. Results and limitations: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 × 10-8) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [pM-I] = 0.004), 8q21.13 (PAG1; pM-I = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; pM-I = 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44-1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers. Conclusions: We report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other established risk factors, has the potential to inform future screening efforts for bladder cancer. Patient summary: We identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with lifestyle risk factors, such as smoking, may inform future preventive and screening strategies for bladder cancer.es_ES
dc.description.peerreviewedNoes_ES
dc.description.sponsorshipThis work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics (ZIA CP010187-18) . The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, and contracts from the Division of Cancer Prevention, National Cancer Institute. Funding for the Nijmegen Bladder Cancer Study was supported by intramural research investment funds from Radboud University Medical Center. Work in the laboratory of Francisco X. Real is funded by Fundacion Cientifica de la Asociacion Espanola Contra el Cancer. The CNIO/UROMOL study and analyses are supported by EU-7FP (HEALTH-F2-2008-201663) and Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (#PI18/01347) . The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II Nutrition Cohort. The Womens Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 396414, and 1074383, and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the Australian Cancer Database. The funding bodies played no direct role in the study. This work was partially supported by The V Foundation for Cancer Research and The Cycle for Survival grants to Vijai Joseph and Helena Furberg. In addition, this research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 to Memorial Sloan Kettering Cancer Center.es_ES
dc.format.number1es_ES
dc.format.page127es_ES
dc.format.volume84es_ES
dc.identifier.citationEur Urol . 2023;84(1):127-137.es_ES
dc.identifier.doi10.1016/j.eururo.2023.04.020es_ES
dc.identifier.e-issn1873-7560es_ES
dc.identifier.journalEuropean urologyes_ES
dc.identifier.pmchttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330197/pdf/nihms-1896587.pdf
dc.identifier.pubmedID37210288es_ES
dc.identifier.urihttps://hdl.handle.net/20.500.12105/23117
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/PI18/01347es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.eururo.2023.04.020es_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Epidemiología Genética y Moleculares_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshUrinary Bladder Neoplasmses_ES
dc.subject.meshArylamine N-Acetyltransferasees_ES
dc.subject.meshMalees_ES
dc.subject.meshHumanses_ES
dc.subject.meshFemalees_ES
dc.subject.meshGenome-Wide Association Studyes_ES
dc.subject.meshProspective Studieses_ES
dc.subject.meshRisk Factorses_ES
dc.subject.meshGenotypees_ES
dc.subject.meshGenetic Predisposition to Diseasees_ES
dc.subject.meshPolymorphism, Single Nucleotidees_ES
dc.subject.meshMicrotubule-Associated Proteinses_ES
dc.subject.meshMembrane Proteinses_ES
dc.subject.meshAdaptor Proteins, Signal Transducinges_ES
dc.titleGenome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insightses_ES
dc.typeresearch articlees_ES
dc.type.hasVersionAMes_ES
dspace.entity.typePublication
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Grupos de investigación
IDIS - Instituto de Investigación Sanitaria de Santiago de Compostela (Galicia)
IIS BioGipuzkoa - Asociación Instituto de Investigación Sanitaria BioGipuzkoa (País Vasco)
IRYCIS - Instituto Ramón y Cajal de Investigación Sanitaria (Madrid)
ISPA - Instituto de Investigación Sanitaria del Principado de Asturias (Asturias)