2026-05-04T19:33:16Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/231172024-11-28T19:29:05Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19597col_20.500.12105_16966col_20.500.12105_16974col_20.500.12105_16988col_20.500.12105_16990
Repisalud author Koutros, Stella author Kiemeney, Lambertus A author Pal Choudhury, Parichoy author Milne, Roger L author Lopez de Maturana, Evangelina author Ye, Yuanqing author Joseph, Vijai author Florez-Vargas, Oscar author Dyrskjøt, Lars author Figueroa, Jonine author Dutta, Diptavo author Giles, Graham G author Hildebrandt, Michelle A T author Offit, Kenneth author Kogevinas, Manolis author Weiderpass, Elisabete author McCullough, Marjorie L author Freedman, Neal D author Albanes, Demetrius author Kooperberg, Charles author Cortessis, Victoria K author Karagas, Margaret R author Johnson, Alison author Schwenn, Molly R author Baris, Dalsu author Furberg, Helena author Bajorin, Dean F author Cussenot, Olivier author Cancel-Tassin, Geraldine author Benhamou, Simone author Kraft, Peter author Porru, Stefano author Carta, Angela author Bishop, Timothy author Southey, Melissa C author Matullo, Giuseppe author Fletcher, Tony author Kumar, Rajiv author Taylor, Jack A author Lamy, Philippe author Prip, Frederik author Kalisz, Mark author Weinstein, Stephanie J author Hengstler, Jan G author Selinski, Silvia author Harland, Mark author Teo, Mark author Kiltie, Anne E author Tardón, Adonina author Serra, Consol author Carrato, Alfredo author García-Closas, Reina author Lloreta, Josep author Schned, Alan author Lenz, Petra author Riboli, Elio author Brennan, Paul author Tjønneland, Anne author Otto, Thomas author Ovsiannikov, Daniel author Volkert, Frank author Vermeulen, Sita H author Aben, Katja K author Galesloot, Tessel E author Turman, Constance author De Vivo, Immaculata author Giovannucci, Edward author Hunter, David J author Hohensee, Chancellor author Hunt, Rebecca author Patel, Alpa V author Huang, Wen-Yi author Thorleifsson, Gudmar author Gago-Dominguez, Manuela author Amiano, Pilar author Golka, Klaus author Stern, Mariana C author Yan, Wusheng author Liu, Jia author Li, Shengchao Alfred author Katta, Shilpa author Hutchinson, Amy author Hicks, Belynda author Wheeler, William A author Purdue, Mark P author McGlynn, Katherine A author Kitahara, Cari M author Haiman, Christopher A author Greene, Mark H author Rafnar, Thorunn author Chatterjee, Nilanjan author Chanock, Stephen J author Wu, Xifeng author Real, Francisco X author Silverman, Debra T author Garcia-Closas, Montserrat author Stefansson, Kari author Prokunina-Olsson, Ludmila author Malats, Nuria author Rothman, Nathaniel funder NIH - National Cancer Institute (NCI) (Estados Unidos) funder Asociación Española Contra el Cáncer funder Instituto de Salud Carlos III funder National Health and Medical Research Council (Australia) funder Radboud University Medical Center funder Canadian Institutes of Health Research (CIHR) Cancer Council Victoria 2024-09-16T08:17:11Z 2024-09-16T08:17:11Z 2023-07 Eur Urol . 2023;84(1):127-137. 10.1016/j.eururo.2023.04.020 1873-7560 European urology https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330197/pdf/nihms-1896587.pdf 37210288 https://hdl.handle.net/20.500.12105/23117 Background: 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. eng Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights research article