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Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization
F. Gálvez-Montosa, G. Peduzzi, JM. Sanchez-Maldonado, R. Ter Horst, AJ. Cabrera-Serrano, M. Gentiluomo, A. Macauda, N. Luque, P. Ünal, FJ. García-Verdejo, Y. Li, JA. López López, A. Stein, HB. Bueno-de-Mesquita, PG. Arcidiacono, DL. Zanette, C....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, metaanalýza
Grantová podpora
GACR21-27902 and AZVNU21-03-00145
Czech Republic Ministry of Health
"Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo
PY20/01282
Consejería de Transformación Económica, Industria, Conocimiento y Universidades and FEDER
PI17/02256
Instituto de Salud Carlos III
PI20/01845
Instituto de Salud Carlos III
26343
Associazione Italiana Ricerca Cancro
LX22NPO5102
National Institute for Cancer Research (Programme EXCELES)
UNCE/MED/006
Charles University, Project GA UK No. 120
PubMed
39319538
DOI
10.1002/ijc.35196
Knihovny.cz E-zdroje
- MeSH
- autofagie * genetika MeSH
- běloši genetika MeSH
- duktální karcinom pankreatu * genetika patologie MeSH
- forkhead transkripční faktory MeSH
- genetická predispozice k nemoci * MeSH
- hepatocytární jaderný faktor 3-alfa genetika metabolismus MeSH
- jednonukleotidový polymorfismus * MeSH
- kohortové studie MeSH
- lidé MeSH
- nádorové biomarkery * genetika MeSH
- nádorové supresorové proteiny * genetika MeSH
- nádory slinivky břišní * genetika patologie MeSH
- studie případů a kontrol MeSH
- transkripční faktory genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.
ARC Net Centre for Applied Research on Cancer University of Verona Verona Italy
Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Cancer Center Amsterdam Imaging and Biomarkers Amsterdam The Netherlands
Carol Davila University of Medicine and Pharmacy Bucharest Romania
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Vienna Austria
Center for Translational Medicine Semmelweis University Budapest Hungary
Centre for Individualised Infection Medicine Hannover Germany
Consortium for Biomedical Research in Epidemiology and Public Health Barcelona Spain
Department of Biochemistry and Molecular Biology 1 University of Granada Granada Spain
Department of Biology University of Pisa Pisa Italy
Department of Biomedical Sciences Humanitas University Milan Italy
Department of Diagnostics and Public Health Section of Pathology University of Verona Verona Italy
Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland
Department of DIMED Laboratory Medicine University of Padova Padova Italy
Department of DISCOG University of Padova Padova Italy
Department of Engineering for Innovation in Medicine University of Verona Verona Italy
Department of Gastroenterology IRCCS Humanitas Research Hospital Endoscopic Unit Milan Italy
Department of General Surgery University of Heidelberg Heidelberg Baden Württemberg Germany
Department of Medical Oncology Complejo Hospitalario de Jaén Jaén Spain
Department of Surgery 1 University Hospital Olomouc Olomouc Czech Republic
Department of Surgery Erasmus MC University Medical Center Rotterdam The Netherlands
Digestive and Liver Disease Unit S Andrea Hospital Rome Italy
Digestive Diseases and Liver Transplantation Center Fundeni Clinical Institute Bucharest Romania
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of General and Transplant Surgery Pisa University Hospital Pisa Italy
Division of Pancreatic Diseases Heart and Vascular Center Semmelweis University Budapest Hungary
Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
German Cancer Consortium Heidelberg Germany
Institute for Translational Medicine Medical School University of Pécs Pécs Hungary
Instituto de Investigación Biosanataria Ibs Granada Granada Spain
János Szentágothai Research Center University of Pécs Pécs Hungary
National Institute for Public Health and the Environment Bilthoven The Netherlands
Oncologia Massa Carrara Azienda USL Toscana Nord Ovest Carrara Italy
Pancreatic Unit IRCCS Humanitas Research Hospital Milan Italy
Potenza County Medical Association Potenza Italy
Saarland Cancer Registry Saarbrücken Germany
Toxicogenomics Unit National Institute of Public Health Prague Czech Republic
Citace poskytuje Crossref.org
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