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Differential Induction in Telomerase Activity among Bladder Cancer Patients and Controls on -Radiation

¹ Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; ² Yale University School of Public Health, New Haven, Connecticut; and ³ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana

Requests for reprints: Xifeng Wu, Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Unit 1304, 1155 Pressler Boulevard, Houston, TX 77030. Phone: 712-745-2485; Fax: 713-563-8973. E-mail: xwu{at}mdanderson.org

Expression of telomerase is one of the hallmarks of tumor cells and has been used as a diagnostic biomarker and a therapeutic target in cancer. Novel findings have shown that telomerase activation in normal human epithelial cells may affect expression of several cancer-related genes, such as growth-related genes and c-myc gene, suggesting a possible role of telomerase in tumor initiation. Therefore, we hypothesized that individuals who are sensitive to mutagen challenge in terms of induced telomerase activity might have increased cancer risk. We tested this hypothesis in a bladder cancer case-control study (51 cases and 51 matched controls) by measuring baseline and -radiation–induced telomerase activities in peripheral blood lymphocytes. We found a significantly higher -radiation–induced telomerase activity in bladder cancer cases compared with the controls (1.34 versus 1.23; P = 0.044). A similar finding was also observed using the normalized telomerase activity (ratio of -radiation induced versus baseline; 1.49 versus 1.19; P < 0.001). In further categorizing the telomerase activity using 75% of the normalized value in the controls as a cutoff point, we found a significantly increased risk for bladder cancer associated with higher induced telomerase activity (adjusted odds ratio, 3.62; 95% confidence interval, 1.38-9.51). In quartile analysis, a dose-response association was noted between the induced telomerase activity and increased bladder cancer risk (P_trend = 0.005). Our findings provide the first evidence linking the mutagen-induced telomerase activity in peripheral blood lymphocytes to the risk of bladder cancer, which warrants further investigation in large-sized studies and other cancer types. (Cancer Epidemiol Biomarkers Prev 2007;16(3):606–9)