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

作者：Stella Koutros, Lambertus A. Kiemeney, Parichoy Pal Choudhury, Roger L. Milne, Evangelina López de Maturana, Yuanqing Ye, Joseph Vijai, Oscar Flórez-Vargas, Lars Dyrskjøt, Jonine D. Figueroa, Diptavo Dutta, Graham G. Giles, Michelle A.T. Hildebrandt, Kenneth Offit, Manolis Kogevinas, Elisabete Weiderpass, Marjorie L. McCullough, Neal D. Freedman, Demetrius Albanes, Charles Kooperberg, Victoria K. Cortessis, Margaret R. Karagas, Alison Johnson, Molly Schwenn, Dalsu Baris, Helena Furberg, Dean F. Bajorin, Olivier Cussenot, Géraldine Cancel‐Tassin, Simone Benhamou, Peter Kraft, Stefano Porru, Angela Carta, D. Timothy Bishop, Melissa C. Southey, Giuseppe Matullo, Tony Fletcher, Rajiv Kumar, Jack A. Taylor, Philippe Lamy, Frederik Prip, Mark Kalisz, Stephanie J. Weinstein, Jan G. Hengstler, Silvia Selinski, Mark Harland, Mark Teo, Anne E. Kiltie, Adonina Tardón, Cònsol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Alan R. Schned, Petra H. Lenz, Elio Ríboli, Paul Brennan, Anne Tjønneland, T. Otto, Д Ю Овсянников, Frank Volkert, Sita H. Vermeulen, Katja K.H. Aben, Tessel E. Galesloot, Constance Turman, Immaculata De Vivo, Edward Giovannucci, David J. Hunter, Chancellor Hohensee, Rebecca Hunt, Alpa V. Patel, Wen‐Yi Huang, Guðmar Þorleifsson, Manuela Gago-Domínguez, Pilar Amiano, Klaus Golka, Mariana C. Stern, Wusheng Yan, Jia Liu, Shengchao Alfred Li, Shilpa Katta, Amy Hutchinson, Belynda Hicks, William A. Wheeler, Mark P. Purdue, Katherine A. McGlynn, Cari M. Kitahara, Christopher A. Haiman, Mark H. Greene, Þórunn Rafnar, Nilanjan Chatterjee, Stephen J. Chanock, Xifeng Wu, Francisco X. Real, Debra T. Silverman, Montserrat García‐Closas, Kāri Stefánsson, Ludmila Prokunina‐Olsson, Núria Malats, Nathaniel Rothman · 发表于：European Urology · 年份：2023 · DOI：10.1016/j.eururo.2023.04.020 · 被引用次数：75 · 研究领域：Bladder and Urothelial Cancer Treatments、Genetic Associations and Epidemiology、Glutathione Transferases and Polymorphisms

Our study identified multiple novel loci associated with bladder cancer susceptibility, bringing the number of independent markers at genome-wide significance to 24. Genetic susceptibility markers, coupled with lifestyle risk factors such as smoking, could guide future preventive measures and screening strategies for bladder cancer. Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. Data from 32 studies that includes 13,790 bladder cancer cases and 343, 502 controls of European ancestry were used for meta-analysis. 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. 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 m...