Función telomérica y sirtuinas 1 y 6 en cáncer colorrectal en pacientes obesos y no obesos. Correlaciones clínicas

Telomere dysfunction is a frequent event in colorectal cancer (CRC). The aim of this study consists of analyzing telomere status and sirtuins 1 and 6, in relation to the prognosis of patients affected by CRC. We have also investigated the possible relationship between obesity and the predisposition to develop CRC. Telomere function parameters, such as telomere length and telomerase activity, as well as the relative expression of SIRT1 and SIRT6 in samples of colorectal tumor tissue, non-tumor tissue (control), and subcutaneous and omental adipose tissues have been investigated. The telomere length was determined by TRF (Telomere Restriction Fragment) and quantitative PCR (qRT-PCR). The relative expression of SIRT1 and SIRT6 was assessed by qRT-PCR. The critically shortened tumor telomeres were associated with a favorable clinical prognosis in CRC and correlate with the higher expression levels of SIRT1. Reduced expression of SIRT1 (RQ ≤ 0.5) was detected in tumors that confer a more adverse clinical evolution. The telomeres of the non-tumor cells from obese or overweight patients were significantly longer than those of patients showing normal weight. In omental adipose tissue, telomere length was lower in obese patients with CRC than in obese patients without CRC. Analyses of the telomeric length and SIRT1 seem of interest in the investigation of the clinical evolution of subjects affected by CRC and in the establishment of the predisposition of obese individuals to the development of this tumor type.