Abstract 4133: Is mitochondrial DNA copy number associated with interval colorectal cancers

Abstract

Abstract Colorectal cancers diagnosed in the interval after a complete colonoscopy (interval colorectal cancers) may occur due to due to rapid tumor growth. We have previously demonstrated that microsatellite instability (MSI) is associated with interval colorectal cancers. Mitochondrial DNA copy number has been shown to be inversely associated with rapid tumor growth in lung and breast cancers. However, the association of mitochondrial DNA copy number with interval colorectal cancers, MSI and survival remains unknown. The aim of our study was to study the association of mitochondrial DNA copy number with interval colorectal cancers, MSI and 5-year survival. We conducted a case-control study of 63 interval and 131 frequency matched non-interval colorectal cancers at the Veterans Administration Medical Center. Interval colorectal cancers were defined as colorectal cancers that developed within 5 years of a complete colonoscopy. Archived tumor specimens were tested for mitochondrial DNA copy number and MSI status. Relative mitochondrial DNA copy number was measured by a quantitative real-time polymerase chain reaction (PCR) assay using two pairs of primers, one specific for amplification of the mitochondria- specific gene (ND1) and another specific for amplification of a nuclear gene (CD3). Multivariable logistic regression was used to evaluate the association between mitochondrial DNA copy number, MSI and interval colorectal cancers. Cox proportional hazards regression was used to evaluate the association between mitochondrial DNA copy number and survival. Median mitochondrial copy number was 5.11 (range 1.4-193). Assay reproducibility, based on 20 samples run in duplicate, was 11%. There was no association between mitochondrial DNA copy number and interval colorectal cancers (OR 0.9; 95% CI 0.66-1.22; p 0.50), but mitochondrial DNA copy number was inversely associated with MSI status (OR 0.32; 95% CI 0.18-0.55; p <.001). There was a trend towards lower overall 5-year survival with lower copy number (HR 0.89; 95% CI 0.74-1.08; p 0.07), and a significantly lower survival with lower copy number among stage IV colorectal cancers (HR 0.53; 95% CI 0.31-0.90; p 0.02). Mitochondrial DNA copy number is inversely associated with MSI and overall survival for colorectal cancer. Low mitochondrial DNA copy number may be a marker of rapid tumor growth and poor survival in colorectal cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4133. doi:10.1158/1538-7445.AM2011-4133