title: Genetic Variants in the Wnt/β-Catenin Signaling Pathway as Indicators of Bladder Cancer Risk.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Department of Epidemiology and Division of Surgery, Department of Urology (AMK, CPND), University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jeanne A
authors.initials: JA
authors.lastname: Pierzynski
authors.affiliation: Department of Epidemiology and Division of Surgery, Department of Urology (AMK, CPND), University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hildebrandt
authors.affiliation: Department of Epidemiology and Division of Surgery, Department of Urology (AMK, CPND), University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
authors.affiliation: Department of Epidemiology and Division of Surgery, Department of Urology (AMK, CPND), University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Epidemiology and Division of Surgery, Department of Urology (AMK, CPND), University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Epidemiology and Division of Surgery, Department of Urology (AMK, CPND), University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Colin P N
authors.initials: CP
authors.lastname: Dinney
authors.affiliation: 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.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012016:Reference Values; D001743:Urinary Bladder / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin
keywords: Wnt signaling pathway; beta catenin; polymorphism; risk; single nucleotide; urinary bladder neoplasms