ArticleInternational journal of cancer2026
ULK4 and CDKN2A polymorphisms influence the risk of developing monoclonal gammopathy of undetermined significance.
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Article in International journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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55 authors.
José Manuel Sánchez-MaldonadoGenomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain.
Angelica MacaudaGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Antonio José Cabrera-SerranoGenomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain.
Hauke ThomsenMSB Medical School Berlin, Berlin, Germany.
Murat GülerGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Rob Ter HorstDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Bethany van GuelpenDepartment of Diagnostics and Intervention, Oncology Unit, Umeå University, Umeå, Sweden.ORCID https://orcid.org/0000-0002-9692-101X
Pavel VodickaDepartment of the Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
Stefano LandiDepartment of Biology, University of Pisa, Pisa, Italy.ORCID https://orcid.org/0000-0001-8364-6357
Subhayan ChattopadhyayDivision of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Pelin ÜnalGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Lucía Ruiz-DuránGenomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain.
Delphine CasabonneUnit of Infections and Cancer, Cancer Epidemiology Research Programme, IDIBELL, Catalan Institute of Oncology, l'Hospitalet de Llobregat, Spain.ORCID https://orcid.org/0000-0002-7874-3707
Hartmut GoldschmidtHeidelberg University, Heidelberg, Germany.
Istemi SerinIstanbul Basaksehir Cam and Sakura City Hospital, Department of Hematology and Adult Bone Marrow Transplantation Unit, University of Health Sciences, Istanbul, Turkey.
María Carretero-FernándezGenomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain.
Elena CabezudoHematolog, Catalan Institute of Oncology, l'Hospitalet de Llobregat, Spain.
Fernando Reyes-ZuritaDepartment of Biochemistry and Molecular Biology I, University of Granada, Granada, Spain.
Aaron D NormanDivision of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.
Ramón García-SanzCIBERONC, Institute of Cancer and Hematological Diseases, Gregorio Marañón General, Madrid, Spain.
Gabriele CapursoPancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Per HoffmannInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Ulrika Pettersson-KymmerClinical Pharmacology, Department of Pharmacology and Clinical Neuroscience, Umea University, Umea, Sweden.
Francisco Jiménez-RomeraGenomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain.
S Vincent RajkumarDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Niels WeinholdDepartment of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
Ludmila VodickovaDepartment of the Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
Christian LangerKempten Clinic, Kempten, Germany.
Angelika SteinGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abdulkadir KarismazDepartment of Hematology, University of Health Sciences, Istanbul Training and Research Hospital, Istanbul, Turkey.
Victor MorenoOncology Data Analytics Program, Catalan Institute of Oncology (ICO), Hospitalet de Llobregat, Barcelona, Spain.ORCID https://orcid.org/0000-0002-2818-5487
Markus M NöthenInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Karl-Heinz JöckelInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Francesca TavanoDivision of Gastroenterology and Endoscopy, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy.ORCID https://orcid.org/0000-0002-8831-7349
Joaquín Martínez-LópezHospital Universitario 12 de Octubre, University Complutense, CIBER-ONC CB16/12/00369, CNIO, Madrid, Spain.
Shaji K KumarDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Juan Francisco Gutiérrez-BautistaInstituto de Investigación Biosanataria IBs.Granada, Granada, Spain.
Daniela BassoDepartment of Medicine, University of Padova Medicina di Laboratorio, Padova, Italy.
Florentin SpäthDepartment of Diagnostics and Intervention, Cancer Center, Hematology, Umeå University, Umeå, Sweden.
Yolanda BenaventeUnit of Infections and Cancer, Cancer Epidemiology Research Programme, IDIBELL, Catalan Institute of Oncology, l'Hospitalet de Llobregat, Spain.
Michelle A T HildebrandtDepartment of Lymphoma-Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID https://orcid.org/0000-0001-6769-6872
Börge SchmidtInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.ORCID https://orcid.org/0000-0001-6948-7273
Tereza SevcikovaDepartment of Hematooncology, University Hospital Ostrava, Ostrava, Czech Republic.
Rui Manuel Vieira ReisLife and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal and ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.ORCID https://orcid.org/0000-0002-9639-7940
Yang LiDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Miguel Ángel López-NevotInstituto de Investigación Biosanataria IBs.Granada, Granada, Spain.
Mihai G NeteaDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Daniele CampaDepartment of Biology, University of Pisa, Pisa, Italy.ORCID https://orcid.org/0000-0003-3220-9944
Alyssa Clay-GilmourDepartment of Biostatistics and Epidemiology, Arnold School of Public Health, University of South Caroline, Greenville, South Carolina, USA.
Susan L SlagerDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Rochester, Minnesota, USA.
Kari HemminkiDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Celine M VachonHospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Spain.
Asta FörstiDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.ORCID https://orcid.org/0000-0002-9857-4728
Federico CanzianGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID https://orcid.org/0000-0002-4261-4583
Juan SainzGenomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS, Granada, Spain.ORCID https://orcid.org/0000-0002-9355-2423
Funding
Consejería de Transformación Económica, Industria, Conocimiento y Universidades and FEDER PY20/01282Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), action GenriskCRIS Foundation against cancer, the Cancer Network of Excellence RD12/10Red de CáncerDietmar Hopp Foundation, and the German Ministry of Education and Science BMBF: CLIOMMICS [01ZX1309]European Union's Horizon 2020 research and innovation programme 856620Instituto de Salud Carlos III CIBERESP CB06/02/0073Instituto de Salud Carlos III DTS23/00030Instituto de Salud Carlos III FI21/00090Instituto de Salud Carlos III PI17/02256Instituto de Salud Carlos III PI20/00288Instituto de Salud Carlos III PI20/01845Italian Ministry of Health through the Ricerca Corrente program 2025-2027National Cancer Institute of the National Institutes of Health R01CA186646National Cancer Institute of the National Institutes of Health U01CA249955National Cancer Institute of the National Institutes of Health U01CA271014SALVAGE CZ.02.01.01/00/22_008/0004644Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia 2021SGR01354Universidad de Granada/CBUA
Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is a necessary precursor condition to multiple myeloma (MM). Given the role of autophagy in modulating MM risk, we investigated whether genetic variation in autophagy-related genes influences susceptibility to MGUS. We analyzed the association of 34,042 common autophagy-related single nucleotide polymorphisms (SNPs) with MGUS across six independent cohorts, five from Europe and one from North America, comprising 2317 MGUS cases and 282,358 controls. We also assessed their impact on immune parameters, including absolute counts of 91 blood-derived immune cell subsets and 103 circulating immunological proteins. Meta-analysis revealed a genome-wide significant association between the ULK4
Indexed as
Cyclin-Dependent Kinase Inhibitor p16Intracellular Signaling Peptides and ProteinsMonoclonal Gammopathy of Undetermined SignificancePolymorphism, Single NucleotideProtein Serine-Threonine KinasesAgedAutophagyCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedCDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p16Intracellular Signaling Peptides and ProteinsProtein Serine-Threonine Kinasesautophagyblood‐derived cell populationsgenetic variantsMGUSsusceptibility
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