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dc.contributor.authorSainz, Juan
dc.contributor.authorGarcía-Verdejo, Francisco José
dc.contributor.authorMartínez-Bueno, Manuel
dc.contributor.authorKumar, Abhishek
dc.contributor.authorSánchez-Maldonado, José Manuel
dc.contributor.authorDíez-Villanueva, Anna
dc.contributor.authorVodičková, Ludmila
dc.contributor.authorVymetálková, Veronika
dc.contributor.authorMartin Sánchez, Vicente
dc.contributor.authorDa Silva Filho, Miguel Inacio
dc.contributor.authorSampaio-Marques, Belém
dc.contributor.authorBrezina, Stefanie
dc.contributor.authorButterbach, Katja
dc.contributor.authorTer Horst, Rob
dc.contributor.authorHoffmeister, Michael
dc.contributor.authorLudovico, Paula
dc.contributor.authorJurado, Manuel
dc.contributor.authorLi, Yang
dc.contributor.authorSánchez-Rovira, Pedro
dc.contributor.authorNetea, Mihai G
dc.contributor.authorGsur, Andrea
dc.contributor.authorVodička, Pavel
dc.contributor.authorMoreno, Víctor
dc.contributor.authorHemminki, Kari
dc.contributor.authorBrenner, Hermann
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorFörsti, Asta
dc.date.accessioned2021-04-23T15:13:26Z
dc.date.available2021-04-23T15:13:26Z
dc.date.issued2021-03-12
dc.identifier.citationCancers (Basel). 2021 Mar 12;13(6):1258. doi: 10.3390/cancers13061258.en_US
dc.identifier.issn2072-6694
dc.identifier.pmid33809172
dc.identifier.doi10.3390/cancers13061258
dc.identifier.urihttp://hdl.handle.net/10033/622842
dc.description.abstractThe 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.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectautophagyen_US
dc.subjectcolorectal canceren_US
dc.subjectgenetic variantsen_US
dc.subjectsusceptibilityen_US
dc.titlePolymorphisms within Autophagy-Related Genes Influence the Risk of Developing Colorectal Cancer: A Meta-Analysis of Four Large Cohorts.en_US
dc.typeArticleen_US
dc.contributor.departmentCiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.en_US
dc.identifier.journalCancersen_US
dc.source.volume13
dc.source.issue6
refterms.dateFOA2021-04-23T15:13:27Z
dc.source.journaltitleCancers
dc.source.countrySwitzerland


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International