Polymorphisms within Autophagy-Related Genes Influence the Risk of Developing Colorectal Cancer: A Meta-Analysis of Four Large Cohorts.
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Authors
Sainz, JuanGarcía-Verdejo, Francisco José
Martínez-Bueno, Manuel
Kumar, Abhishek
Sánchez-Maldonado, José Manuel
Díez-Villanueva, Anna
Vodičková, Ludmila
Vymetálková, Veronika
Martin Sánchez, Vicente
Da Silva Filho, Miguel Inacio
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, Víctor
Hemminki, Kari
Brenner, Hermann
Chang-Claude, Jenny
Försti, Asta
Issue Date
2021-03-12
Metadata
Show full item recordAbstract
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.Citation
Cancers (Basel). 2021 Mar 12;13(6):1258. doi: 10.3390/cancers13061258.Affiliation
CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.Publisher
MDPIJournal
CancersPubMed ID
33809172Type
ArticleLanguage
enISSN
2072-6694ae974a485f413a2113503eed53cd6c53
10.3390/cancers13061258
Scopus Count
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- Creative Commons