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Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization
E. Clavero, JM. Sanchez-Maldonado, A. Macauda, R. Ter Horst, B. Sampaio-Marques, A. Jurczyszyn, A. Clay-Gilmour, A. Stein, MAT. Hildebrandt, N. Weinhold, G. Buda, R. García-Sanz, W. Tomczak, U. Vogel, A. Jerez, D. Zawirska, M. Wątek, JN. Hofmann,...
Jazyk angličtina Země Švýcarsko
Typ dokumentu metaanalýza, časopisecké články
Grantová podpora
PI17/02256
Instituto de Salud Carlos III
PI20/01845
Instituto de Salud Carlos III
RD12/10 Red de Cáncer
the CRIS foundation against cancer, from the Cancer Network of Excellence
BMBF: CLIOMMICS [01ZX1309]
the Dietmar Hopp Foundation and the German Ministry of Education and Science
R01CA186646
National Cancer Institute of the National Institutes of Health
U01CA249955 (EEB)
National Cancer Institute of the National Institutes of Health
NLK
Free Medical Journals
od 2000
Freely Accessible Science Journals
od 2000
PubMed Central
od 2007
Europe PubMed Central
od 2007
ProQuest Central
od 2000-03-01
Open Access Digital Library
od 2000-01-01
Open Access Digital Library
od 2007-01-01
Health & Medicine (ProQuest)
od 2000-03-01
ROAD: Directory of Open Access Scholarly Resources
od 2000
PubMed
37239846
DOI
10.3390/ijms24108500
Knihovny.cz E-zdroje
- MeSH
- autofagie MeSH
- biologické markery MeSH
- imunoglobulin M MeSH
- leukocyty mononukleární patologie MeSH
- lidé MeSH
- mnohočetný myelom * genetika patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10-9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10-4-5.79 × 10-14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10-4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10-4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10-4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3- B cells, CD5+IgD- cells, IgM- cells, IgD-IgM- cells, and CD4-CD8- PBMCs (p = 4.9 × 10-4-8.6 × 10-4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27- cells (p = 9.3 × 10-4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3-, MCP-2-, and IL20-dependent pathways.
Cancer Control Research BC Cancer Vancouver BC V5Z 4E6 Canada
Cancer Epidemiology Division Cancer Council Victoria Melbourne VIC 3004 Australia
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences 1090 Vienna Austria
Centre for Individualised Infection Medicine 30625 Hannover Germany
Department of Biochemistry and Molecular Biology 1 University of Granada 18071 Granada Spain
Department of Biology University of Pisa 56126 Pisa Italy
Department of Cancer Prevention and Therapy Wroclaw Medical University 50 367 Wroclaw Poland
Department of Hematology and Transplantology Medical University of Gdansk 80 210 Gdansk Poland
Department of Hematology Hospital del Mar 08003 Barcelona Spain
Department of Hematology Medical University of Lodz 90 419 Lodz Poland
Department of Hematology Military Institute of Medicine 04 141 Warsaw Poland
Department of Hematology Odense University Hospital DK 5000 Odense Denmark
Department of Hematology Rigshospitalet Copenhagen University DK 2100 Copenhagen Denmark
Department of Hematology Rydygier Hospital 31 826 Cracow Poland
Department of Hematology University Hospital 30 688 Kraków Poland
Department of Hematology University Hospital No 2 85 168 Bydgoszcz Poland
Department of Internal Medicine 5 University of Heidelberg 69120 Heidelberg Germany
Department of Medical Oncology Complejo Hospitalario de Jaén 23007 Jaén Spain
Department of Medicine University of Granada 18012 Granada Spain
Division of Epidemiology Department of Health Sciences Research Mayo Clinic Rochester MN 55902 USA
Division of Hematology Department of Internal Medicine Mayo Clinic Rochester MN 55902 USA
Division of Hematology Huntsman Cancer Institute University of Utah Salt Lake City UT 84112 USA
Division of Pediatric Neurooncology German Cancer Research Center 69120 Heidelberg Germany
Division of Population Oncology BC Cancer Vancouver BC V5Z 4E6 Canada
Genomic Epidemiology Group German Cancer Research Center 69120 Heidelberg Germany
Hematology Department Virgen de las Nieves University Hospital 18012 Granada Spain
Hematology Division Chaim Sheba Medical Center Tel Hashomer 52621 Israel
Holycross Medical Oncology Center 25 735 Kielce Poland
Hopp Children's Cancer Center 69120 Heidelberg Germany
Hospital 12 de Octubre Complutense University CNIO CIBERONC 28041 Madrid Spain
Institute of Bioinformatics International Technology Park Bangalore 560066 India
Institute of Hematology and Transfusion Medicine 00 791 Warsaw Poland
Instituto de Investigación Biosanataria IBs Granada 18014 Granada Spain
Manipal Academy of Higher Education Manipal 576104 India
Molecular Oncology Research Center Barretos Cancer Hospital Barretos 14784 400 Brazil
Myeloma Institute University of Arkansas for Medical Sciences Little Rock AR 72205 USA
National Research Centre for the Working Environment DK 2100 Copenhagen Denmark
School of Population and Public Health University of British Columbia Vancouver BC V6T 1Z4 Canada
Semmelweis University 1083 Budapest Hungary
St Johns Hospital 62769 Budapest Hungary
U O Dipartimento di Ematologia Azienda USL Toscana Nord Ovest 57124 Livorno Italy
UMR INSERM 1052 CNRS 5286 University of Lyon Hospices Civils de Lyon 69008 Lyon France
Citace poskytuje Crossref.org
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