Jeanne A Pierzynski1, Michelle A Hildebrandt1, Ashish M Kamat1, Jie Lin1, Yuanqing Ye1, Colin P N Dinney1, Xifeng Wu2. 1. Department of Epidemiology and Division of Surgery, Department of Urology (AMK, CPND), University of Texas M.D. Anderson Cancer Center, Houston, Texas. 2. Department of Epidemiology and Division of Surgery, Department of Urology (AMK, CPND), University of Texas M.D. Anderson Cancer Center, Houston, Texas. Electronic address: xwu@mdanderson.org.
Abstract
PURPOSE: Genetic factors that influence bladder cancer risk remain largely unknown. Previous research has suggested that there is a strong genetic component underlying the risk of bladder cancer. The Wnt/β-catenin signaling pathway is a key modulator of cellular proliferation through its regulation of stem cell homeostasis. Furthermore, variants in the Wnt/β-catenin signaling pathway have been implicated in the development of other cancers, leading us to believe that this pathway may have a vital role in bladder cancer development. MATERIALS AND METHODS: A total of 230 single nucleotide polymorphisms in 40 genes in the Wnt/β-catenin signaling pathway were genotyped in 803 bladder cancer cases and 803 healthy controls. RESULTS: A total of 20 single nucleotide polymorphisms were nominally significant for risk. Individuals with 2 variants of LRP6: rs10743980 were associated with a decreased risk of bladder cancer in the recessive model in the initial analysis (OR 0.76, 95% CI 0.58-0.99, p=0.039). This was validated using the bladder genome-wide association study chip (OR 0.51, 95% CI 0.27-1.00, p=0.049 and for combined analysis p=0.007). CONCLUSIONS: Together these findings implicate variants in the Wnt/β-catenin stem cell pathway as having a role in bladder cancer etiology.
PURPOSE: Genetic factors that influence bladder cancer risk remain largely unknown. Previous research has suggested that there is a strong genetic component underlying the risk of bladder cancer. The Wnt/β-catenin signaling pathway is a key modulator of cellular proliferation through its regulation of stem cell homeostasis. Furthermore, variants in the Wnt/β-catenin signaling pathway have been implicated in the development of other cancers, leading us to believe that this pathway may have a vital role in bladder cancer development. MATERIALS AND METHODS: A total of 230 single nucleotide polymorphisms in 40 genes in the Wnt/β-catenin signaling pathway were genotyped in 803 bladder cancer cases and 803 healthy controls. RESULTS: A total of 20 single nucleotide polymorphisms were nominally significant for risk. Individuals with 2 variants of LRP6: rs10743980 were associated with a decreased risk of bladder cancer in the recessive model in the initial analysis (OR 0.76, 95% CI 0.58-0.99, p=0.039). This was validated using the bladder genome-wide association study chip (OR 0.51, 95% CI 0.27-1.00, p=0.049 and for combined analysis p=0.007). CONCLUSIONS: Together these findings implicate variants in the Wnt/β-catenin stem cell pathway as having a role in bladder cancer etiology.
Authors: Montserrat Garcia-Closas; Yuanqing Ye; Nathaniel Rothman; Jonine D Figueroa; Núria Malats; Colin P Dinney; Nilanjan Chatterjee; Ludmila Prokunina-Olsson; Zhaoming Wang; Jie Lin; Francisco X Real; Kevin B Jacobs; Dalsu Baris; Michael Thun; Immaculata De Vivo; Demetrius Albanes; Mark P Purdue; Manolis Kogevinas; Ashish M Kamat; Seth P Lerner; H Barton Grossman; Jian Gu; Xia Pu; Amy Hutchinson; Yi-Ping Fu; Laurie Burdett; Meredith Yeager; Wei Tang; Adonina Tardón; Consol Serra; Alfredo Carrato; Reina García-Closas; Josep Lloreta; Alison Johnson; Molly Schwenn; Margaret R Karagas; Alan Schned; Gerald Andriole; Robert Grubb; Amanda Black; Eric J Jacobs; W Ryan Diver; Susan M Gapstur; Stephanie J Weinstein; Jarmo Virtamo; David J Hunter; Neil Caporaso; Maria Teresa Landi; Joseph F Fraumeni; Debra T Silverman; Stephen J Chanock; Xifeng Wu Journal: Hum Mol Genet Date: 2011-08-08 Impact factor: 6.150
Authors: Meng Chen; Michelle A T Hildebrandt; Jessica Clague; Ashish M Kamat; Antoni Picornell; Joshua Chang; Xiaofan Zhang; Julie Izzo; Hushan Yang; Jie Lin; Jian Gu; Stephen Chanock; Manolis Kogevinas; Nathaniel Rothman; Debra T Silverman; Montserrat Garcia-Closas; H Barton Grossman; Colin P Dinney; Núria Malats; Xifeng Wu Journal: Cancer Prev Res (Phila) Date: 2010-09-21
Authors: Nathaniel Rothman; Montserrat Garcia-Closas; Nilanjan Chatterjee; Nuria Malats; Xifeng Wu; Jonine D Figueroa; Francisco X Real; David Van Den Berg; Giuseppe Matullo; Dalsu Baris; Michael Thun; Lambertus A Kiemeney; Paolo Vineis; Immaculata De Vivo; Demetrius Albanes; Mark P Purdue; Thorunn Rafnar; Michelle A T Hildebrandt; Anne E Kiltie; Olivier Cussenot; Klaus Golka; Rajiv Kumar; Jack A Taylor; Jose I Mayordomo; Kevin B Jacobs; Manolis Kogevinas; Amy Hutchinson; Zhaoming Wang; Yi-Ping Fu; Ludmila Prokunina-Olsson; Laurie Burdett; Meredith Yeager; William Wheeler; Adonina Tardón; Consol Serra; Alfredo Carrato; Reina García-Closas; Josep Lloreta; Alison Johnson; Molly Schwenn; Margaret R Karagas; Alan Schned; Gerald Andriole; Robert Grubb; Amanda Black; Eric J Jacobs; W Ryan Diver; Susan M Gapstur; Stephanie J Weinstein; Jarmo Virtamo; Victoria K Cortessis; Manuela Gago-Dominguez; Malcolm C Pike; Mariana C Stern; Jian-Min Yuan; David J Hunter; Monica McGrath; Colin P Dinney; Bogdan Czerniak; Meng Chen; Hushan Yang; Sita H Vermeulen; Katja K Aben; J Alfred Witjes; Remco R Makkinje; Patrick Sulem; Soren Besenbacher; Kari Stefansson; Elio Riboli; Paul Brennan; Salvatore Panico; Carmen Navarro; Naomi E Allen; H Bas Bueno-de-Mesquita; Dimitrios Trichopoulos; Neil Caporaso; Maria Teresa Landi; Federico Canzian; Borje Ljungberg; Anne Tjonneland; Francoise Clavel-Chapelon; David T Bishop; Mark T W Teo; Margaret A Knowles; Simonetta Guarrera; Silvia Polidoro; Fulvio Ricceri; Carlotta Sacerdote; Alessandra Allione; Geraldine Cancel-Tassin; Silvia Selinski; Jan G Hengstler; Holger Dietrich; Tony Fletcher; Peter Rudnai; Eugen Gurzau; Kvetoslava Koppova; Sophia C E Bolick; Ashley Godfrey; Zongli Xu; José I Sanz-Velez; María D García-Prats; Manuel Sanchez; Gabriel Valdivia; Stefano Porru; Simone Benhamou; Robert N Hoover; Joseph F Fraumeni; Debra T Silverman; Stephen J Chanock Journal: Nat Genet Date: 2010-10-24 Impact factor: 38.330