Please use this identifier to cite or link to this item:
Title: Polymorphisms within Autophagy-Related Genes Influence the Risk of Developing Colorectal Cancer: A Meta-Analysis of Four Large Cohorts
Author: Sainz, Juan
García Verdejo, Francisco José
Martínez Bueno, Manuel
Kumar, Abhishek
Sánchez Maldonado, José Manuel
Díez Villanueva, Anna
Vodičková, Ludmila
Vymetálková, Veronika
Martín Sánchez, Vicente
Silva Filho, Miguel Inacio Da
Sampaio Marques, Belém
Brezina, Stefanie
Butterbach, Katja
Ter Horst, Rob
Hoffmeister, Michael
Ludovico, Paula
Jurado, Manuel
Li, Yang
Sánchez Rovira, Pedro
Netea, Mihai G.
Gsur, Andrea
Vodička, Pavel
Moreno Aguado, Víctor
Hemminki, Kari
Brenner, Hermann
Chang-Claude, Jenny
Försti, Asta
Keywords: Càncer colorectal
Colorectal cancer
Issue Date: 12-Mar-2021
Publisher: MDPI
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.
Note: Reproducció del document publicat a:
It is part of: Cancers, 2021, vol. 13, num. 6
Related resource:
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
cancers-13-01258-v3.pdf1.6 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons