Abstract
The risk of colorectal cancer (CRC) development has been associated with telomere dysfunction and obesity. However, clinical relevance of these parameters in CRC prognosis is not clear. Therefore, the aim of the present 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. According to published data, this is the first work in which obesity and telomere status are jointly considered in relation to CRC prognosis. A prospective study including 162 patients with CRC submitted to curative surgical treatment was performed. Subjects were classified according to their BMI. Telomere status was established through telomere length and telomerase activity evaluation. Statistical analyses were performed using the SPSS software package version 22. Telomere shortening was inversely associated with BMI in patients with CRC. Notably, among patients with CRC, subjects with obesity exhibited less shortening of tumor telomeres than non-obese patients (P=0.047). 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, regardless of the Dukes' stage of cancers (P=0.025, for tumor samples; P=0.003, for non-tumor samples). Additionally, subjects with a BMI >31.85 kg/m2 showed the worse clinical outcomes compared with subjects with other BMI values. Interestingly, the impact of BMI showed sex dependence, since only the group of men displayed significant differences in CRC prognosis in relation to obesity status (P=0.037). From the results of the present study, based on a multivariate prediction model to establish prognosis, it was concluded that telomere length is a useful biomarker to predict prognosis in patients with CRC. Regardless of BMI values, the improved clinical evolution was associated with shorter telomeres. The impact of BMI seems to be associated with other factors, such as sex.
Highlights
Obesity is an emerging and increasingly prevalent condition in the Western world
Thence, the relationship between body mass index (BMI) and risk of colorectal cancer (CRC) has been the focus of several investigations [4,5], and these studies have shown that an increase in BMI is related to a higher incidence of CRC
Of all 162 CRC patients included in this study, 82 were females and 80 males, with a mean age of 70.6±0.9 years
Summary
Obesity is an emerging and increasingly prevalent condition in the Western world. It is associated with well‐known metabolic disorders, leading to the development of different diseases, including cancer [1]. The increase in white adipose tissue (WAT) affects the development of the disease due to the release of several adipokines, interleukins and other cytokines by this type of tissue [2]. These factors cause greater hormonal signaling, increased proliferation and survival of adjacent and distal cells which could induce tumorigenesis [3]. Only few of the publications have shown poorer results for patients with obesity [6,7] and, the relationship between obesity and the prognosis of CRC has not been widely studied
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