Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization
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,...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/10/8500 |
| _version_ | 1797599896912527360 |
|---|---|
| author | Esther Clavero José Manuel Sanchez-Maldonado Angelica Macauda Rob Ter Horst Belém Sampaio-Marques Artur Jurczyszyn Alyssa Clay-Gilmour Angelika Stein Michelle A. T. Hildebrandt Niels Weinhold Gabriele Buda Ramón García-Sanz Waldemar Tomczak Ulla Vogel Andrés Jerez Daria Zawirska Marzena Wątek Jonathan N. Hofmann Stefano Landi John J. Spinelli Aleksandra Butrym Abhishek Kumar Joaquín Martínez-López Sara Galimberti María Eugenia Sarasquete Edyta Subocz Elzbieta Iskierka-Jażdżewska Graham G. Giles Malwina Rybicka-Ramos Marcin Kruszewski Niels Abildgaard Francisco García Verdejo Pedro Sánchez Rovira Miguel Inacio da Silva Filho Katalin Kadar Małgorzata Razny Wendy Cozen Matteo Pelosini Manuel Jurado Parveen Bhatti Marek Dudzinski Agnieszka Druzd-Sitek Enrico Orciuolo Yang Li Aaron D. Norman Jan Maciej Zaucha Rui Manuel Reis Miroslaw Markiewicz Juan José Rodríguez Sevilla Vibeke Andersen Krzysztof Jamroziak Kari Hemminki Sonja I. Berndt Vicent Rajkumar Grzegorz Mazur Shaji K. Kumar Paula Ludovico Arnon Nagler Stephen J. Chanock Charles Dumontet Mitchell J. Machiela Judit Varkonyi Nicola J. Camp Elad Ziv Annette Juul Vangsted Elizabeth E. Brown Daniele Campa Celine M. Vachon Mihai G. Netea Federico Canzian Asta Försti Juan Sainz |
| author_facet | Esther Clavero José Manuel Sanchez-Maldonado Angelica Macauda Rob Ter Horst Belém Sampaio-Marques Artur Jurczyszyn Alyssa Clay-Gilmour Angelika Stein Michelle A. T. Hildebrandt Niels Weinhold Gabriele Buda Ramón García-Sanz Waldemar Tomczak Ulla Vogel Andrés Jerez Daria Zawirska Marzena Wątek Jonathan N. Hofmann Stefano Landi John J. Spinelli Aleksandra Butrym Abhishek Kumar Joaquín Martínez-López Sara Galimberti María Eugenia Sarasquete Edyta Subocz Elzbieta Iskierka-Jażdżewska Graham G. Giles Malwina Rybicka-Ramos Marcin Kruszewski Niels Abildgaard Francisco García Verdejo Pedro Sánchez Rovira Miguel Inacio da Silva Filho Katalin Kadar Małgorzata Razny Wendy Cozen Matteo Pelosini Manuel Jurado Parveen Bhatti Marek Dudzinski Agnieszka Druzd-Sitek Enrico Orciuolo Yang Li Aaron D. Norman Jan Maciej Zaucha Rui Manuel Reis Miroslaw Markiewicz Juan José Rodríguez Sevilla Vibeke Andersen Krzysztof Jamroziak Kari Hemminki Sonja I. Berndt Vicent Rajkumar Grzegorz Mazur Shaji K. Kumar Paula Ludovico Arnon Nagler Stephen J. Chanock Charles Dumontet Mitchell J. Machiela Judit Varkonyi Nicola J. Camp Elad Ziv Annette Juul Vangsted Elizabeth E. Brown Daniele Campa Celine M. Vachon Mihai G. Netea Federico Canzian Asta Försti Juan Sainz |
| author_sort | Esther Clavero |
| collection | DOAJ |
| description | 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; <i>p</i> < 1 × 10<sup>−9</sup>) 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, <i>CD46</i>, <i>IKBKE</i>, <i>PARK2</i>, <i>ULK4</i>, <i>ATG5</i>, and <i>CDKN2A</i> associated with MM risk (<i>p</i> = 4.47 × 10<sup>−4</sup>−5.79 × 10<sup>−14</sup>). Mechanistically, we found that the <i>ULK4</i><sub>rs6599175</sub> SNP correlated with circulating concentrations of vitamin D3 (<i>p</i> = 4.0 × 10<sup>−4</sup>), whereas the <i>IKBKE</i><sub>rs17433804</sub> SNP correlated with the number of transitional CD24<sup>+</sup>CD38<sup>+</sup> B cells (<i>p</i> = 4.8 × 10<sup>−4</sup>) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (<i>p</i> = 3.6 × 10<sup>−4</sup>). We also found that the <i>CD46</i><sub>rs1142469</sub> SNP correlated with numbers of CD19<sup>+</sup> B cells, CD19<sup>+</sup>CD3<sup>−</sup> B cells, CD5<sup>+</sup>IgD<sup>−</sup> cells, IgM<sup>−</sup> cells, IgD<sup>−</sup>IgM<sup>−</sup> cells, and CD4<sup>−</sup>CD8<sup>−</sup> PBMCs (<i>p</i> = 4.9 × 10<sup>−4</sup>−8.6 × 10<sup>−4</sup>) and circulating concentrations of interleukin (IL)-20 (<i>p</i> = 0.00082). Finally, we observed that the <i>CDKN2A</i><sub>rs2811710</sub> SNP correlated with levels of CD4<sup>+</sup>EMCD45RO<sup>+</sup>CD27<sup>−</sup> cells (<i>p</i> = 9.3 × 10<sup>−4</sup>). 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<sup>−</sup>, MCP-2<sup>−</sup>, and IL20-dependent pathways. |
| first_indexed | 2024-03-11T03:40:49Z |
| format | Article |
| id | doaj.art-aa9ac778adcb44f8af0c75e4b483b12d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:40:49Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aa9ac778adcb44f8af0c75e4b483b12d2023-11-18T01:36:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410850010.3390/ijms24108500Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional CharacterizationEsther Clavero0José Manuel Sanchez-Maldonado1Angelica Macauda2Rob Ter Horst3Belém Sampaio-Marques4Artur Jurczyszyn5Alyssa Clay-Gilmour6Angelika Stein7Michelle A. T. Hildebrandt8Niels Weinhold9Gabriele Buda10Ramón García-Sanz11Waldemar Tomczak12Ulla Vogel13Andrés Jerez14Daria Zawirska15Marzena Wątek16Jonathan N. Hofmann17Stefano Landi18John J. Spinelli19Aleksandra Butrym20Abhishek Kumar21Joaquín Martínez-López22Sara Galimberti23María Eugenia Sarasquete24Edyta Subocz25Elzbieta Iskierka-Jażdżewska26Graham G. Giles27Malwina Rybicka-Ramos28Marcin Kruszewski29Niels Abildgaard30Francisco García Verdejo31Pedro Sánchez Rovira32Miguel Inacio da Silva Filho33Katalin Kadar34Małgorzata Razny35Wendy Cozen36Matteo Pelosini37Manuel Jurado38Parveen Bhatti39Marek Dudzinski40Agnieszka Druzd-Sitek41Enrico Orciuolo42Yang Li43Aaron D. Norman44Jan Maciej Zaucha45Rui Manuel Reis46Miroslaw Markiewicz47Juan José Rodríguez Sevilla48Vibeke Andersen49Krzysztof Jamroziak50Kari Hemminki51Sonja I. Berndt52Vicent Rajkumar53Grzegorz Mazur54Shaji K. Kumar55Paula Ludovico56Arnon Nagler57Stephen J. Chanock58Charles Dumontet59Mitchell J. Machiela60Judit Varkonyi61Nicola J. Camp62Elad Ziv63Annette Juul Vangsted64Elizabeth E. Brown65Daniele Campa66Celine M. Vachon67Mihai G. Netea68Federico Canzian69Asta Försti70Juan Sainz71Hematology Department, Virgen de las Nieves University Hospital, 18012 Granada, SpainGenomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, 18016 Granada, SpainGenomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, PortugalPlasma Cell Dyscrasias Center, Department of Hematology, Jagiellonian University Medical College, 31-066 Kraków, PolandDepartment of Biostatistics and Epidemiology, Arnold School of Public Health, University of South Carolina, Greenville, SC 29208, USAGenomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDepartment of Lymphoma–Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAMyeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USAHaematology Unit, Department of Clinical and Experimental Medicine, University of Pisa/AOUP, 56126 Pisa, ItalyDiagnostic Laboratory Unit in Hematology, University Hospital of Salamanca, IBSAL, CIBERONC, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), 37007 Salamanca, SpainDepartment of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-059 Lublin, PolandNational Research Centre for the Working Environment, DK-2100 Copenhagen, DenmarkDepartment of Hematology, Experimental Hematology Unit, Vall d’Hebron Institute of Oncology (VHIO), University Hospital Vall d’Hebron, 08035 Barcelona, SpainDepartment of Hematology, University Hospital, 30-688 Kraków, PolandHolycross Medical Oncology Center, 25-735 Kielce, PolandDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USADepartment of Biology, University of Pisa, 56126 Pisa, ItalyDivision of Population Oncology, BC Cancer, Vancouver, BC V5Z 4E6, CanadaDepartment of Cancer Prevention and Therapy, Wroclaw Medical University, 50-367 Wroclaw, PolandInstitute of Bioinformatics, International Technology Park, Bangalore 560066, IndiaHospital 12 de Octubre, Complutense University, CNIO, CIBERONC, 28041 Madrid, SpainHaematology Unit, Department of Clinical and Experimental Medicine, University of Pisa/AOUP, 56126 Pisa, ItalyDiagnostic Laboratory Unit in Hematology, University Hospital of Salamanca, IBSAL, CIBERONC, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), 37007 Salamanca, SpainDepartment of Hematology, Military Institute of Medicine, 04-141 Warsaw, PolandDepartment of Hematology, Medical University of Lodz, 90-419 Lodz, PolandCancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, AustraliaDepartment of Hematology, Specialist Hospital No. 1 in Bytom, Academy of Silesia, Faculty of Medicine, 40-055 Katowice, PolandDepartment of Hematology, University Hospital No. 2, 85-168 Bydgoszcz, PolandDepartment of Hematology, Odense University Hospital, DK-5000 Odense, DenmarkDepartment of Medical Oncology, Complejo Hospitalario de Jaén, 23007 Jaén, SpainDepartment of Medical Oncology, Complejo Hospitalario de Jaén, 23007 Jaén, SpainDivision of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, GermanySt Johns Hospital, 62769 Budapest, HungaryDepartment of Hematology, Rydygier Hospital, 31-826 Cracow, PolandDivision of Hematology/Oncology, Department of Medicine, School of Medicine, Department of Pathology, School of Medicine, Susan and Henry Samueli College of Health Sciences, Chao Family Comprehensive Cancer Center, University of California at Irvine, Irvine, CA 92697, USAU.O. Dipartimento di Ematologia, Azienda USL Toscana Nord Ovest, 57124 Livorno, ItalyHematology Department, Virgen de las Nieves University Hospital, 18012 Granada, SpainCancer Control Research, BC Cancer, Vancouver, BC V5Z 4E6, CanadaDepartment of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, 35-310 Rzeszow, PolandDepartment of Lymphoproliferative Diseases, Maria Skłodowska Curie National Research Institute of Oncology, 02-781 Warsaw, PolandHaematology Unit, Department of Clinical and Experimental Medicine, University of Pisa/AOUP, 56126 Pisa, ItalyDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDivision of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55902, USADepartment of Hematology and Transplantology, Medical University of Gdansk, 80-210 Gdansk, PolandLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal and ICVS/3B’s-PT Government Associate Laboratory, 4710-057 Braga/Guimarães, PortugalDepartment of Hematology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, 35-310 Rzeszow, PolandDepartment of Hematology, Hospital del Mar, 08003 Barcelona, SpainMolecular Diagnostics and Clinical Research Unit, Institute of Regional Health Research, University Hospital of Southern Denmark, DK-6200 Aabenraa, DenmarkDepartment of Hematology, Transplantology and Internal Medicine, Medical University of Warsaw, 02-097 Warsaw, PolandDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, GermanyDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USADivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902, USADepartment of Internal Diseases, Occupational Medicine, Hypertension and Clinical Oncology, Wroclaw Medical University, 50-368 Wroclaw, PolandDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902, USALife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, PortugalHematology Division, Chaim Sheba Medical Center, Tel Hashomer 52621, IsraelDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAUMR INSERM 1052/CNRS 5286, University of Lyon, Hospices Civils de Lyon, 69008 Lyon, FranceDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USASemmelweis University, 1083 Budapest, HungaryDivision of Hematology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USADepartment of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94143, USADepartment of Hematology, Rigshospitalet, Copenhagen University, DK-2100 Copenhagen, DenmarkDepartment of Pathology, Heersink School of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Biology, University of Pisa, 56126 Pisa, ItalyDivision of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55902, USADepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsGenomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, GermanyGenomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS, 18016 Granada, SpainMultiple 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; <i>p</i> < 1 × 10<sup>−9</sup>) 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, <i>CD46</i>, <i>IKBKE</i>, <i>PARK2</i>, <i>ULK4</i>, <i>ATG5</i>, and <i>CDKN2A</i> associated with MM risk (<i>p</i> = 4.47 × 10<sup>−4</sup>−5.79 × 10<sup>−14</sup>). Mechanistically, we found that the <i>ULK4</i><sub>rs6599175</sub> SNP correlated with circulating concentrations of vitamin D3 (<i>p</i> = 4.0 × 10<sup>−4</sup>), whereas the <i>IKBKE</i><sub>rs17433804</sub> SNP correlated with the number of transitional CD24<sup>+</sup>CD38<sup>+</sup> B cells (<i>p</i> = 4.8 × 10<sup>−4</sup>) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (<i>p</i> = 3.6 × 10<sup>−4</sup>). We also found that the <i>CD46</i><sub>rs1142469</sub> SNP correlated with numbers of CD19<sup>+</sup> B cells, CD19<sup>+</sup>CD3<sup>−</sup> B cells, CD5<sup>+</sup>IgD<sup>−</sup> cells, IgM<sup>−</sup> cells, IgD<sup>−</sup>IgM<sup>−</sup> cells, and CD4<sup>−</sup>CD8<sup>−</sup> PBMCs (<i>p</i> = 4.9 × 10<sup>−4</sup>−8.6 × 10<sup>−4</sup>) and circulating concentrations of interleukin (IL)-20 (<i>p</i> = 0.00082). Finally, we observed that the <i>CDKN2A</i><sub>rs2811710</sub> SNP correlated with levels of CD4<sup>+</sup>EMCD45RO<sup>+</sup>CD27<sup>−</sup> cells (<i>p</i> = 9.3 × 10<sup>−4</sup>). 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<sup>−</sup>, MCP-2<sup>−</sup>, and IL20-dependent pathways.https://www.mdpi.com/1422-0067/24/10/8500multiple myelomaautophagygenetic variantsgenetic susceptibility |
| spellingShingle | Esther Clavero José Manuel Sanchez-Maldonado Angelica Macauda Rob Ter Horst Belém Sampaio-Marques Artur Jurczyszyn Alyssa Clay-Gilmour Angelika Stein Michelle A. T. Hildebrandt Niels Weinhold Gabriele Buda Ramón García-Sanz Waldemar Tomczak Ulla Vogel Andrés Jerez Daria Zawirska Marzena Wątek Jonathan N. Hofmann Stefano Landi John J. Spinelli Aleksandra Butrym Abhishek Kumar Joaquín Martínez-López Sara Galimberti María Eugenia Sarasquete Edyta Subocz Elzbieta Iskierka-Jażdżewska Graham G. Giles Malwina Rybicka-Ramos Marcin Kruszewski Niels Abildgaard Francisco García Verdejo Pedro Sánchez Rovira Miguel Inacio da Silva Filho Katalin Kadar Małgorzata Razny Wendy Cozen Matteo Pelosini Manuel Jurado Parveen Bhatti Marek Dudzinski Agnieszka Druzd-Sitek Enrico Orciuolo Yang Li Aaron D. Norman Jan Maciej Zaucha Rui Manuel Reis Miroslaw Markiewicz Juan José Rodríguez Sevilla Vibeke Andersen Krzysztof Jamroziak Kari Hemminki Sonja I. Berndt Vicent Rajkumar Grzegorz Mazur Shaji K. Kumar Paula Ludovico Arnon Nagler Stephen J. Chanock Charles Dumontet Mitchell J. Machiela Judit Varkonyi Nicola J. Camp Elad Ziv Annette Juul Vangsted Elizabeth E. Brown Daniele Campa Celine M. Vachon Mihai G. Netea Federico Canzian Asta Försti Juan Sainz Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization International Journal of Molecular Sciences multiple myeloma autophagy genetic variants genetic susceptibility |
| title | Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization |
| title_full | Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization |
| title_fullStr | Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization |
| title_full_unstemmed | Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization |
| title_short | Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization |
| title_sort | polymorphisms within autophagy related genes as susceptibility biomarkers for multiple myeloma a meta analysis of three large cohorts and functional characterization |
| topic | multiple myeloma autophagy genetic variants genetic susceptibility |
| url | https://www.mdpi.com/1422-0067/24/10/8500 |
| work_keys_str_mv | AT estherclavero polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT josemanuelsanchezmaldonado polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT angelicamacauda polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT robterhorst polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT belemsampaiomarques polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT arturjurczyszyn polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT alyssaclaygilmour polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT angelikastein polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT michelleathildebrandt polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT nielsweinhold polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT gabrielebuda polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT ramongarciasanz polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT waldemartomczak polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT ullavogel polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT andresjerez polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT dariazawirska polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT marzenawatek polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT jonathannhofmann polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT stefanolandi polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT johnjspinelli polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT aleksandrabutrym polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT abhishekkumar polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT joaquinmartinezlopez polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT saragalimberti polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT mariaeugeniasarasquete polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT edytasubocz polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT elzbietaiskierkajazdzewska polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT grahamggiles polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT malwinarybickaramos polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT marcinkruszewski polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT nielsabildgaard polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT franciscogarciaverdejo polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT pedrosanchezrovira polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT miguelinaciodasilvafilho polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT katalinkadar polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT małgorzatarazny polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT wendycozen polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT matteopelosini polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT manueljurado polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT parveenbhatti polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT marekdudzinski polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT agnieszkadruzdsitek polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT enricoorciuolo polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT yangli polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT aarondnorman polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT janmaciejzaucha polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT ruimanuelreis polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT miroslawmarkiewicz polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT juanjoserodriguezsevilla polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT vibekeandersen polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT krzysztofjamroziak polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT karihemminki polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT sonjaiberndt polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT vicentrajkumar polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT grzegorzmazur polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT shajikkumar polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT paulaludovico polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT arnonnagler polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT stephenjchanock polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT charlesdumontet polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT mitchelljmachiela polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT juditvarkonyi polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT nicolajcamp polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT eladziv polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT annettejuulvangsted polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT elizabethebrown polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT danielecampa polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT celinemvachon polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT mihaignetea polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT federicocanzian polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT astaforsti polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization AT juansainz polymorphismswithinautophagyrelatedgenesassusceptibilitybiomarkersformultiplemyelomaametaanalysisofthreelargecohortsandfunctionalcharacterization |