Polymorphisms within Autophagy-Related Genes Influence the Risk of Developing Colorectal Cancer: A Meta-Analysis of Four Large Cohorts
Year: 2021
Type: review
Abstract: The role of genetic variation in autophagy-related genes in modulating autophagy and cancer is poorly understood. Here, we comprehensively investigated the association of autophagy-related variants with colorectal cancer (CRC) risk and provide new insights about the molecular mechanisms underlying the associations. After meta-analysis of the genome-wide association study (GWAS) data from four independent European cohorts (8006 CRC cases and 7070 controls), two loci, DAPK2 (p = 2.19 × 10−5) and ATG5 (p = 6.28 × 10−4) were associated with the risk of CRC. Mechanistically, the DAPK2rs11631973G allele was associated with IL1 β levels after the stimulation of peripheral blood mononuclear cells (PBMCs) with Staphylococcus aureus (p = 0.002), CD24 + CD38 + CD27 + IgM + B cell levels in blood (p = 0.0038) and serum levels of en-RAGE (p = 0.0068). ATG5rs546456T allele was associated with TNF α and IL1 β levels after the stimulation of PBMCs with LPS (p = 0.0088 and p = 0.0076, respectively), CD14+CD16− cell levels in blood (p = 0.0068) and serum levels of CCL19 and cortisol (p = 0.0052 and p = 0.0074, respectively). Interestingly, no association with autophagy flux was observed. These results suggested an effect of the DAPK2 and ATG5 loci in the pathogenesis of CRC, likely through the modulation of host immune responses.
Source: Cancers
Authors: Juan Sainz, Francisco José García-Verdejo, Manuel Martínez-Bueno, Abhishek Kumar, José Manuel Sánchez-Maldonado, Anna Díez-Villanueva, Ludmila Vodičková, Veronika Vymetálková, Vicente Martin Sánchez, Miguel Inacio Da Silva Filho, Belém Sampaio-Marques, Stefanie Brezina, Katja Butterbach, Rob ter Horst, Michael Hoffmeister, Paula Ludovico, Manuel Jurado, Yang Li, Pedro Sánchez-Rovira, Mihai G. Netea, Andrea Gsur, Pavel Vodička, Víctor Moreno, Kari Hemminki, Hermann Brenner, Jenny Chang-Claude, Asta Försti
Institutions: Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Hospital Universitario Virgen de las Nieves, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Complejo Hospitalario de Jaén, Manipal Academy of Higher Education, German Cancer Research Center, Institute of Bioinformatics, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Universitat de Barcelona, Czech Academy of Sciences, Charles University, Czech Academy of Sciences, Institute of Experimental Medicine, Universidad de León, University of Minho, Medical University of Vienna, Heidelberg University, Radboud University Nijmegen, Radboud University Medical Center, Medizinische Hochschule Hannover, Helmholtz Centre for Infection Research, Centre for Individualised Infection Medicine, Center for Experimental and Clinical Infection Research, University of Bonn, National Center for Tumor Diseases, University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Hopp Children's Cancer Center Heidelberg, Deutsches Konsortium für Translationale Krebsforschung
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,376
Awards: ERA Chair Position for Excellent Research in Oncology, Estudio de las interacciones microbioma-anfitrión para la prevención del cáncer colorrectal (Colonbiome), Identificación de marcadores de susceptibilidad genética útiles para el diseño de estrategias personalizadas de cribado, G6255981358, G7789535379
OpenAlex ID: W3137630216