%0 Journal Article
%A Sainz, Juan
%A García-Verdejo, Francisco José
%A Martínez-Bueno, Manuel
%A Kumar, Abhishek
%A Sánchez-Maldonado, José Manuel
%A Díez-Villanueva, Anna
%A Vodičková, Ludmila
%A Vymetálková, Veronika
%A Martin Sánchez, Vicente
%A Da Silva Filho, Miguel Inacio
%A Sampaio-Marques, Belém
%A Brezina, Stefanie
%A Butterbach, Katja
%A Ter Horst, Rob
%A Hoffmeister, Michael
%A Ludovico, Paula
%A Jurado, Manuel
%A Li, Yang
%A Sánchez-Rovira, Pedro
%A Netea, Mihai G
%A Gsur, Andrea
%A Vodička, Pavel
%A Moreno, Víctor
%A Hemminki, Kari
%A Brenner, Hermann
%A Chang-Claude, Jenny
%A Försti, Asta
%T Polymorphisms within Autophagy-Related Genes Influence the Risk of Developing Colorectal Cancer: A Meta-Analysis of Four Large Cohorts.
%D 2021
%@ 2072-6694
%U http://hdl.handle.net/10668/17510
%X 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.
%K autophagy
%K colorectal cancer
%K genetic variants
%K susceptibility
%~