title: Role of CYP1B1 gene polymorphisms in bladder cancer susceptibility.
abstract: OBJECTIVE
  CYP1B1 activates procarcinogens in some human tissues, including the urinary tract. Changes related to genetic polymorphisms are a known risk factor for cancer. We analyzed the association between CYP1B1 sequence variations and bladder cancer.
  
  
  METHODS
  Sequence variations in the coding region (exons 2 and 3) and the neighboring introns of CYP1B1 were analyzed by direct polymerase chain reaction and DNA sequencing in 208 unrelated patients with bladder cancer and 208 healthy controls.
  
  
  RESULTS
  We identified 6 known single nucleotide polymorphisms organized into 2 linkage disequilibrium blocks. The Ala/Ala and Leu/Val genotypes of the Ala119Ser and Leu432Val polymorphisms were significantly more common in patients than in controls (55.3% vs 42.8% and 54.8% vs 42.3%, respectively). The strongest individual single nucleotide polymorphism risk was found under an over dominant model for Leu432Val (OR 1.65, CI 95% 1.12-2.44). The 2 susceptibility single nucleotide polymorphisms were predicted to be structured into 4 haplotypes and more than 10 diplotypes. No individual haplotype was associated with bladder cancer but the diplotype Ala-Leu/Ala-Val was significantly overrepresented in cases compared to controls (31.73% vs 17.31%, OR 2.22, 95% CI 1.36-3.62, p = 0.001). The OR was approximately 1.6 for the individual genotypes Ala/Ala and Leu/Val, which increased to 2.2 for the Ala-Leu/Ala-Val diplotype. A risk occupation had a modifying effect, increasing the crude OR of the combined genotype Ala/Ala + Leu/Val from 2.2 to 8.3.
  
  
  CONCLUSIONS
  This study provides strong evidence for the role of common CYP1B1 variants as risk factors for bladder cancer, which increases with occupational exposure.
authors.affiliation: Urology Department, University of Castilla-La Mancha, Albacete, Spain. asalinas@pulso.com
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Salinas-Sánchez
authors.forename: María J
authors.initials: MJ
authors.lastname: Donate-Moreno
authors.forename: María-Pilar
authors.initials: MP
authors.lastname: López-Garrido
authors.forename: José M
authors.initials: JM
authors.lastname: Giménez-Bachs
authors.forename: Julio
authors.initials: J
authors.lastname: Escribano
mesh_terms: D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D003430:Cross-Sectional Studies; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1