389 GAMMA-H2AX LEVEL IN PERIPHERAL BLOOD LYMPHOCYTES AS A RISK PREDICTOR FOR BLADDER CANCER

Abstract

You have accessJournal of UrologyUrothelial Cancer: Natural History, Markers & Pathophysiology1 Apr 2013389 GAMMA-H2AX LEVEL IN PERIPHERAL BLOOD LYMPHOCYTES AS A RISK PREDICTOR FOR BLADDER CANCER Mario Fernandez, Yilei Gong, Yuanqing Ye, Jie Lin, David Chang, Ashish Kamat, and Xifeng Wu Mario FernandezMario Fernandez Houston, TX More articles by this author , Yilei GongYilei Gong Houston, TX More articles by this author , Yuanqing YeYuanqing Ye Houston, TX More articles by this author , Jie LinJie Lin Houston, TX More articles by this author , David ChangDavid Chang Houston, TX More articles by this author , Ashish KamatAshish Kamat Houston, TX More articles by this author , and Xifeng WuXifeng Wu Houston, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1778AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Identification of susceptibility to double-strand breaks (DSB) may provide valuable information about genomic instability and cancer risk. The formation of gamma-H2AX foci is a highly sensitive marker for DNA DSBs induction. We assessed whether levels of gamma-H2AX in peripheral blood lymphocytes (PBL) obtained after stimulation by ionizing radiation (IR) are associated with bladder cancer risk in a bladder cancer case-control study. METHODS Patients and controls were enrolled from an ongoing bladder cancer case-control study. Epidemiologic data were collected during an in-person interview using a structured questionnaire. Baseline and IR induced H2AX-phosphorylation was assessed in PBL from 174 newly diagnosed, previously untreated bladder cancer patients and from 174 age, sex and ethnicity - matched, healthy control subjects by a novel, image-based, high-throughput phenotypic assay. The ratio of gamma-H2AX level of IR-treated cells to that of non-treated cells (baseline) derived from the same blood sample was used as the parameter to assess the sensitivity to the mutagen. We built two different risk models; the epidemiologic model included only demographic variables (age, sex and smoking status) whereas mutagen sensitivity assessment was added to the second model. Receiver operating characteristic curves were constructed and the area under curve (AUC) was used to evaluate model discriminatory ability. RESULTS The mean gamma-H2AX ratios were significantly higher for cases than for controls (1.43±0.14 vs. 1.35±0.12; p=1.44E-08). This trend was irrespective of age, sex or smoking status. The risk estimates of bladder cancer for induced DNA DSBs by tertile distributions in controls showed a significant trend for increased risk at the highest tertiles for the whole cohort (OR=3.09; 95%CI 1.76-5.40; p=8.15E-05 for the second tertile and OR=3.78; 95%CI 2.26-6.33; p=4.18E-07 for the third tertile) as well as for each category. Discrimination ability of the epidemiological model was moderate (AUC=0.64). However, the AUC increased significantly to 0.74 when gamma-H2AX ratio was incorporated. CONCLUSIONS Our findings suggest that a higher susceptibility to induction of DSBs as measured by the gamma-H2AX assay is significantly associated with an increased risk for bladder cancer. This might help to identify individuals at high risk for this cancer, adding new perspectives to established epidemiological and genetic risk factors. Further research of the role of gamma-H2AX in biological processes of bladder cancer is warranted. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e157-e158 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mario Fernandez Houston, TX More articles by this author Yilei Gong Houston, TX More articles by this author Yuanqing Ye Houston, TX More articles by this author Jie Lin Houston, TX More articles by this author David Chang Houston, TX More articles by this author Ashish Kamat Houston, TX More articles by this author Xifeng Wu Houston, TX More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...