Abstract
Abstract Introduction: 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. Material and 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. Logistic regression analysis was used to estimate odds ratios associated with gamma-H2AX. We also compared the discriminatory ability of a model with only demographic variables and a model including gamma-H2AX ratio. 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 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, with an area under curve (AUC) of 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. Citation Format: Mario I. Fernandez, Yilei Gong, Yuanqing Ye, Jie Lin, David Chang, Xifeng Wu. Gamma-H2AX level in peripheral blood lymphocytes as a risk predictor for bladder cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 113. doi:10.1158/1538-7445.AM2013-113
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.