Abstract 3658: The association of mitochondrial DNA content with bladder cancer risk and outcome

Abstract

Abstract Mitochondrion plays essential role in energy production and apoptosis process from the initiation to regulation of apoptosis. Many studies have showed the association of dys-regulated mitochondrial DNA (mtDNA) with the development and progression of cancer, aging and longevity, and neurodegenerative diseases. In this study, we will test the hypothesis that variation in mtDNA content (also called mtDNA copy number) may be associated with individual's bladder cancer risk and clinical outcome in a case-control study of 1026 bladder cancer patients and 980 healthy-controls. We will also assess the association of mtDNA content with progression/recurrence in non-muscle invasive bladder cancer (NMIBC) patients and overall survival in muscle invasive and metastatic bladder cancer (MIMBC) patients. Quantitative real-time polymerase chain reaction in peripheral blood lymphocytes was used to measure mtDNA content. We observed significantly lower mtDNA content in bladder cancer patients (mean = 1.05, SD = 0.36) than controls (mean = 1.11, SD = 0.39) with P value < 0.001. When we categorized the mtDNA content using the quartile distribution in controls, Lower mtDNA content (less than 1st quantile) was associated with 1.69-fold increased risk of bladder cancer (95% confidence interval [CI] = 1.17 to 1.68), compared to those who have higher mtDNA content (greater than 4th quartile). In patients with MIMBC, we also observed the significant association of lower mtDNA content with poor survival. After categorizing the mtDNA content using quartile distribution in patients who were alive, there is a significantly increased risk of death for patients with lower mtDNA content (hazard ratio = 1.75, 95% CI = 1.11 to 2.77). There is also a significantly reduced median survival time (44.5 months vs 25.4 months, log-rank P = 0.004). However, there is no significant association of mtDNA content with progression/recurrence in NMIBC patients. In conclusion, low mtDNA content is associated with significantly increased risk of bladder cancer risk and poor survival. The resulted from our study will contribute to personalized risk prediction and may also become potential molecular targets for prevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3658. doi:1538-7445.AM2012-3658