Obesity And Telomere Status In The Prognosis Of Colorectal Cancer Patients Submitted To Curative Intention Surgical Treatment

Abstract

Background The risk of colorectal cancer (CRC) development has been related to telomere dysfunction and obesity. However, prognosis of patients affected by CRC has not clearly established considering both telomere attrition and obesity status. Previous published data highlights the importance of studying how obesity influences telomere function and its potential role as a predictor of prognosis in CRC. The aim of this study was to evaluate the impact of obesity and telomere status in the prognosis of patients affected by CRC and submitted to curative surgical treatment. Methods We performed a prospective study including 162 CRC patients submitted to curative surgical treatment. Samples were obtained from tumor and non-tumor tissues. Subjects were classified according to their Body Mass Index (BMI). Telomere status was established through telomere length and telomerase evaluation. Statistical analyses were performed using the SPSS software package version 22. Differences in two or more groups of study were calculated by parametric or non-parametric tests, depending on normality and homoscedasticity conditions of the variables. Prognosis was analyzed using the Kaplan-Meier method. The potential prognostic impact of the variables considered in this work jointly, was evaluated by Cox multivariate regression analyses. Results Patients with shorter telomeres, both in the tumor (median telomere length < 6.5 kb) and their non-tumor paired tissues (median telomere length < 7.1 kb), had the best clinical evolution, independently of the Dukes' stage of cancers (P = 0.025, for tumor samples; P = 0.003, for non-tumor samples). Telomere shortening was inversely associated with BMI in CRC patients. Also, subjects with a BMI > 31.85kg/m 2 showed the worse clinical outcomes. Of interest, the impact of BMI showed gender dependence, since only the group of men showed significant differences in CRC prognosis in relation to obesity status (P = 0.037). Conclusions Telomere length constitutes a useful biomarker to predict prognosis in CRC. Independently of BMI values, the better clinical evolution was associated with shorter telomeres. Obesity seems to have an impact on the clinical outcomes of CRC; however, the impact of BMI seems to be related to other factors such as gender.