Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/176242
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 Autofàgia Colorectal cancer Autophagy |
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: https://doi.org/10.3390/cancers13061258 |
It is part of: | Cancers, 2021, vol. 13, num. 6 |
URI: | http://hdl.handle.net/2445/176242 |
Related resource: | https://doi.org/10.3390/cancers13061258 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
cancers-13-01258-v3.pdf | 1.6 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License