A pilot study evaluating peripheral blood lymphocyte telomere length in elderly versus young patients with colorectal cancer (CRC).

Abstract

512 Background: Telomere length (TL) is associated with aging as well as high cancer incidence. We conducted a pilot study to assess the TL of younger versus older (≥70 years) patients with CRC and its effect on survival. Methods: QPCR was used to analyze the relationship between telomere repeat copy number and single gene copy number (T/S ratio) on peripheral blood lymphocytes DNA of 94 CRC patients, and used as a surrogate value for relative TL. The primary aim of the study was to evaluate differences in TL between different age groups. Correlation with overall survival (OS) was the secondary aim. Samples were run in triplicate, and a standard curve was used to calculate the relative T/S ratio and account for plate to plate variability. Univariate statistical analyses were performed using the Mann-Whitney test for continuous variables and the log-rank test for OS. Multivariable analyses were performed using the Classification and Regression Trees methodology. A Type I error of 5% was used to determine statistical significance. Results: The mean relative TL was 0.95 (range 0.64-1.84). The assay demonstrated high correlation of technical replicates between plates (Pearson correlation: 0.96 and 0.81, for sample and control). Comparing patient under and over 70 years of age revealed a borderline significant difference in TL between the groups (mean TL 0.981 versus 0.925 respectively; p=0.067). Assessment using 4 age groups (50-60, 60-70, 70-80, >80) demonstrated a statistically significant difference in TL between the youngest and the oldest age groups (mean TL 1.022 versus 0.874 respectively; p=0.02) with evidence of shorter TL with advanced age. Marginal relationship was seen between OS and age (p-value=0.066) with older patients exhibiting slightly poorer survival (hazard ratio of 1.03, 95% confidence interval (0.998, 1.065)). No correlation was noted between relative TL and OS in univariate and multivariable analysis. Conclusions: These results validate the ability of a qPCR-based assay to differentiate between younger and older CRC patients by TL. Ongoing studies are utilizing this methodology to evaluate the relationship of TL to treatment tolerance in elderly CRC patients.