Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/ijms24043526
Keywords
colorectal cancer; early-onset colorectal cancer; risk; screening; telomere length
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The incidence of early-onset colorectal cancer (EOCRC; age younger than 50 years) has been increasing worldwide. This study explored the potential use of telomere length (TL) as a biomarker for EOCRC screening. TL was found to be significantly shorter in EOCRC patients compared to healthy individuals, suggesting a possible association between telomeric shortening and EOCRC susceptibility. Additionally, certain gene variants related to TL maintenance were found to be associated with the risk of developing EOCRC. Germline TL measurement and analysis of telomere maintenance gene polymorphisms could potentially facilitate early identification of individuals at risk of EOCRC.
Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing in recent decades worldwide. The need for new biomarkers for EOCRC prevention strategies is undeniable. In this study, we aimed to explore whether an aging factor, such as telomere length (TL), could be a useful tool in EOCRC screening. The absolute leukocyte TL from 87 microsatellite stable EOCRC patients and 109 healthy controls (HC) with the same range of age, was quantified by Real Time Quantitative PCR (RT-qPCR). Then, leukocyte whole-exome sequencing (WES) was performed to study the status of the genes involved in TL maintenance (hTERT, TERC, DKC1, TERF1, TERF2, TERF2IP, TINF2, ACD, and POT1) in 70 sporadic EOCRC cases from the original cohort. We observed that TL was significantly shorter in EOCRC patients than in healthy individuals (EOCRC mean: 122 kb vs. HC mean: 296 kb; p < 0.001), suggesting that telomeric shortening could be associated with EOCRC susceptibility. In addition, we found a significant association between several SNPs of hTERT (rs79662648), POT1 (rs76436625, rs10263573, rs3815221, rs7794637, rs7784168, rs4383910, and rs7782354), TERF2 (rs251796 and rs344152214), and TERF2IP (rs7205764) genes and the risk of developing EOCRC. We consider that the measurement of germline TL and the status analysis of telomere maintenance related genes polymorphisms at early ages could be non-invasive methods that could facilitate the early identification of individuals at risk of developing EOCRC.
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