Telomere Length as a New Risk Marker of Early-Onset Colorectal Cancer

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), co...

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Detalles Bibliográficos
Autores: Martel Martel, Abel Jesús, Corchete, Luis A., Martí, Marc, Vidal-Tocino, Rosario, Hurtado, Elena, Álvaro, Edurne, Jiménez, Fernando, Jiménez-Toscano, Marta, Balaguer, Francesc, Sanz, Gonzalo, López, Irene, Hernández-Villafranca, Sergio, Ballestero, Araceli, Vivas, Alfredo, Melone, Sirio, Pastor, José Carlos, Brandáriz, Lorena, Gomez-Marcos, Manuel A., Cruz, Juan Jesús, Perea, José, González-Sarmiento, Rogelio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/353131
Acceso en línea:http://hdl.handle.net/10261/353131
Access Level:acceso abierto
Palabra clave:Colorectal cancer
Early-onset colorectal cancer
Risk
Screening
Telomere length
Descripción
Sumario: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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