Leukocyte telomere length throughout the continuum of colorectal carcinogenesis

2018 
// Cornelia Zochmeister 1, * , Stefanie Brezina 1, * , Philipp Hofer 1 , Andreas Baierl 2 , Michael M. Bergmann 3 , Thomas Bachleitner-Hofmann 3 , Judith Karner-Hanusch 3 , Anton Stift 3 , Armin Gerger 4 , Gernot Leeb 5 , Karl Mach 5 , Sivaramakrishna Rachakonda 6 , Rajiv Kumar 6 and Andrea Gsur 1 1 Medical University Vienna, Department of Medicine I, Institute of Cancer Research, Vienna, Austria 2 University of Vienna, Department of Statistics and Operations Research, Vienna, Austria 3 Medical University Vienna, Department of Surgery, Vienna, Austria 4 Medical University of Graz, Division of Oncology, Department of Internal Medicine, Graz, Austria 5 Hospital Oberpullendorf, Burgenland, Austria 6 German Cancer Research Center, Division of Molecular Genetic Epidemiology, Heidelberg, Germany * These authors have contributed equally to this work Correspondence to: Andrea Gsur, email: andrea.gsur@meduniwien.ac.at Keywords: telomere length; colorectal cancer; adenoma; cancer epidemiology Received: September 08, 2017      Accepted: January 31, 2018      Published: February 07, 2018 ABSTRACT Considering the high prevalence of colorectal cancer (CRC) and relatively high mortality there is strong interest in identification of clinically relevant biomarkers. Telomere shortening is supposed to contribute to genomic instability and crucially involved in process of carcinogenesis. Peripheral blood leukocyte (PBL) telomere length was previously investigated in several studies as potential biomarker for CRC but with controversial results. This prompted us to investigate relative PBL telomere length in association with different histological findings throughout the continuum of colorectal carcinogenesis in order to reflect the whole spectrum of putative CRC development in a large study involving 2011 individuals. The study based on the Colorectal Cancer Study of Austria (CORSA), including 384 CRC cases as well as age- and gender-matched 544 high-risk adenomas, 537 low-risk adenoma patients and 546 colonoscopy-negative controls. Relative expression of telomeric repeats and the single copy reference gene, albumin (T/S ratio) was determined using monochrome multiplex quantitative PCR (MMQPCR). Telomeres were found to be significantly longer in CRC patients compared to control subjects ( P = 3.61x10 -6 ). Yet, no significant differences in telomere length could be detected for high-risk ( P = 0.05956) and low-risk colorectal adenoma patients ( P = 0.05224). In addition, results presented in this manuscript highlight the impact of various epidemiological factors on PBL telomere length and its involvement in CRC. However, further large studies also including colorectal adenomas are necessary to confirm these results.
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