BACKGROUND: Cell cycle checkpoint regulation is crucial for the prevention of carcinogenesis in mammalian cells. METHODS: To test the hypothesis that common sequence variants in the cell cycle control pathway may affect bladder cancer susceptibility, the effects of a panel of 10 potential functional single nucleotide polymorphisms (SNPs) from 7 cell cycle control genes, P53, P21, P27, CDK4, CDK6, CCND1, and STK15, were evaluated on bladder cancer risk in a case-control study of 696 bladder cancer cases and 629 healthy controls. RESULTS: Overall, on individual SNP analysis only individuals with the p53 intron 3 16-bp duplication polymorphism variant allele had a significantly reduced bladder cancer risk (odds ratio [OR] = 0.74, 95% confidence interval [CI], 0.56-0.96). This effect was more evident in former smokers and younger subjects. We then applied the Classification and Regression Tree (CART) statistical approach to explore the high-order gene-gene and gene-smoking interactions. In the CART analysis, smoking status was identified as the most influential factor for bladder cancer susceptibility. The final decision tree by CART contained 6 terminal nodes. Compared with the second-lowest risk group the ORs for terminal nodes 1 and 3 to 6 ranged from 0.46 to 6.30. CONCLUSIONS: These results suggest that cell cycle genetic polymorphisms may affect bladder cancer predisposition through modulation of host genome stability and confirm the importance of studying gene-gene and gene-environment interactions in bladder cancer risk assessment. (c) 2008 American Cancer Society.
BACKGROUND: Cell cycle checkpoint regulation is crucial for the prevention of carcinogenesis in mammalian cells. METHODS: To test the hypothesis that common sequence variants in the cell cycle control pathway may affect bladder cancer susceptibility, the effects of a panel of 10 potential functional single nucleotide polymorphisms (SNPs) from 7 cell cycle control genes, P53, P21, P27, CDK4, CDK6, CCND1, and STK15, were evaluated on bladder cancer risk in a case-control study of 696 bladder cancer cases and 629 healthy controls. RESULTS: Overall, on individual SNP analysis only individuals with the p53 intron 3 16-bp duplication polymorphism variant allele had a significantly reduced bladder cancer risk (odds ratio [OR] = 0.74, 95% confidence interval [CI], 0.56-0.96). This effect was more evident in former smokers and younger subjects. We then applied the Classification and Regression Tree (CART) statistical approach to explore the high-order gene-gene and gene-smoking interactions. In the CART analysis, smoking status was identified as the most influential factor for bladder cancer susceptibility. The final decision tree by CART contained 6 terminal nodes. Compared with the second-lowest risk group the ORs for terminal nodes 1 and 3 to 6 ranged from 0.46 to 6.30. CONCLUSIONS: These results suggest that cell cycle genetic polymorphisms may affect bladder cancer predisposition through modulation of host genome stability and confirm the importance of studying gene-gene and gene-environment interactions in bladder cancer risk assessment. (c) 2008 American Cancer Society.
Authors: Annemarie Koch; Jiri Hatina; Harald Rieder; Hans-Helge Seifert; Wolfgang Huckenbeck; Frank Jankowiak; Andrea R Florl; Robert Stoehr; Wolfgang A Schulz Journal: Cell Oncol (Dordr) Date: 2012-06-06 Impact factor: 6.730
Authors: Rebecca A Mason; Elaine V Morlock; Margaret R Karagas; Karl T Kelsey; Carmen J Marsit; Alan R Schned; Angeline S Andrew Journal: Carcinogenesis Date: 2009-04-16 Impact factor: 4.944