RT Journal Article
T1 Polymorphisms within Autophagy-Related Genes Influence the Risk of Developing Colorectal Cancer: A Meta-Analysis of Four Large Cohorts.
A1 Sainz, Juan
A1 García-Verdejo, Francisco José
A1 Martínez-Bueno, Manuel
A1 Kumar, Abhishek
A1 Sánchez-Maldonado, José Manuel
A1 Díez-Villanueva, Anna
A1 Vodičková, Ludmila
A1 Vymetálková, Veronika
A1 Martin Sánchez, Vicente
A1 Da Silva Filho, Miguel Inacio
A1 Sampaio-Marques, Belém
A1 Brezina, Stefanie
A1 Butterbach, Katja
A1 Ter Horst, Rob
A1 Hoffmeister, Michael
A1 Ludovico, Paula
A1 Jurado, Manuel
A1 Li, Yang
A1 Sánchez-Rovira, Pedro
A1 Netea, Mihai G
A1 Gsur, Andrea
A1 Vodička, Pavel
A1 Moreno, Víctor
A1 Hemminki, Kari
A1 Brenner, Hermann
A1 Chang-Claude, Jenny
A1 Försti, Asta
K1 autophagy
K1 colorectal cancer
K1 genetic variants
K1 susceptibility
AB 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.
SN 2072-6694
YR 2021
FD 2021-03-12
LK http://hdl.handle.net/10668/17510
UL http://hdl.handle.net/10668/17510
LA en
DS RISalud
RD Apr 12, 2025