PURPOSE: 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.
MATERIALS AND 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.
Written by:
Salinas-Sánchez AS, Donate-Moreno MJ, López-Garrido MP, Giménez-Bachs JM, Escribano J. Are you the author?
Urology Department, Hospital and University Complex of Albacete and Human Molecular Genetics Laboratory, School of Medicine/Institute for Research in Neurological Disabilities, University of Castilla-La Mancha (MPLG, JE), Albacete, Spain.
Reference: J Urol. 2012 Feb;187(2):700-6. Epub 2011 Dec 16.
PubMed Abstract
PMID: 22177211
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