Benzo(a)pyrene Diol Epoxide-Induced Chromosome 9p21 Aberrations Are Associated with Increased Risk of Bladder Cancer
| Autor: | Colin P.N. Dinney, Xifeng Wu, Jian Gu, Yohei Horikawa, Meng Chen |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Risk Pathology medicine.medical_specialty Epidemiology 7 8-Dihydro-7 8-dihydroxybenzo(a)pyrene 9 10-oxide Chromosome 9 In situ hybridization Biology chemistry.chemical_compound polycyclic compounds Genetic predisposition medicine Humans Chromosome Aberrations Chi-Square Distribution Bladder cancer Case-control study Cancer Odds ratio Middle Aged medicine.disease Logistic Models Urinary Bladder Neoplasms Oncology Benzo(a)pyrene chemistry Case-Control Studies Cancer research Female Chromosomes Human Pair 9 Mutagens |
| Zdroj: | Cancer Epidemiology, Biomarkers & Prevention. 17:2445-2450 |
| ISSN: | 1538-7755 1055-9965 |
| Popis: | Purpose: Loss of chromosome 9p21 is one of the most frequent genomic alterations in bladder cancer. Alterations of 9p21 and p16 are also frequently seen in the epithelial cells of chronic smokers. We hypothesize that 9p21 is a molecular target of benzo(a)pyrene diol epoxide (BPDE), the metabolic product of tobacco carcinogen benzo(a)pyrene, and 9p21 BPDE sensitivity is a genetic susceptibility factor for bladder cancer. Material and Methods: In this case-control study of 203 bladder cancer cases and 198 matched healthy controls, we compared the frequencies of BPDE-induced 9p21 aberrations in cultured peripheral blood lymphocytes using fluorescent in situ hybridization and evaluated the association between 9p21 BPDE sensitivity and bladder cancer risk. Results: We found that BPDE-induced chromosome 9p21 aberrations were significantly higher in peripheral blood lymphocytes of bladder cancer cases (20.76 ± 6.97 per 1,000) than those of controls (16.58 ± 7.07 per 1,000; P < 0.0001). However, no difference was observed for CEP9, a control centromere locus on chromosome 9. Using the median aberration value in the controls as a cutoff point to dichotomize BPDE sensitivity and after adjustment by age, sex, ethnicity, and smoking status, 9p21 BPDE sensitivity was associated with a significantly increased risk of bladder cancer (odds ratio, 5.29; 95% confidence interval, 3.26-8.59), whereas the odds ratio for the CEP9 locus was 0.99 (95% confidence interval, 0.66-1.50). There was also a dose-response relationship between the 9p21 BPDE sensitivity and increased risk for bladder cancer. Conclusion: 9p21 may be a molecular target for BPDE damage in bladder cancer cases and 9p21 BPDE sensitivity may be a marker of bladder cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2445–50) |
| Databáze: | OpenAIRE |
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