{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:04:46Z","timestamp":1773331486125,"version":"3.50.1"},"reference-count":78,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020230","name":"Consejer\u00eda de Transformaci\u00f3n Econ\u00f3mica, Industria, Conocimiento y Universidades","doi-asserted-by":"publisher","award":["PY20\/01282"],"award-info":[{"award-number":["PY20\/01282"]}],"id":[{"id":"10.13039\/100020230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031692","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CIBERESP CB06\/02\/0073"],"award-info":[{"award-number":["CIBERESP CB06\/02\/0073"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["DTS23\/00030"],"award-info":[{"award-number":["DTS23\/00030"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FI21\/00090"],"award-info":[{"award-number":["FI21\/00090"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/02256"],"award-info":[{"award-number":["PI17\/02256"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00288"],"award-info":[{"award-number":["PI20\/00288"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/01845"],"award-info":[{"award-number":["PI20\/01845"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006393","name":"Universidad de Granada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006393","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\u2010related genes influences susceptibility to MGUS. We analyzed the association of 34,042 common autophagy\u2010related 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\u2010derived immune cell subsets and 103 circulating immunological proteins. Meta\u2010analysis revealed a genome\u2010wide significant association between the\n                    <jats:italic>ULK4<\/jats:italic>\n                    <jats:sub>rs6599175C<\/jats:sub>\n                    allele and increased MGUS risk (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20093.35\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ). Carriers of this allele showed reduced counts of memory B cell subsets (IgM+CD38+CD27+ and IgD+IgM+CD27+;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.0038 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.0056, respectively) and natural effector B cells (CD24+CD38+IgD+IgM+ cells;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.0060). Although these associations were not statistically significant after multiple testing correction, they suggest a role of\n                    <jats:italic>ULK4<\/jats:italic>\n                    in early B\u2010cell differentiation. Additionally, the\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    <jats:sub>rs2811710<\/jats:sub>\n                    variant showed a suggestive association with MGUS risk (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20092.17\u2009\u00d7\u200910\n                    <jats:sup>\u22124<\/jats:sup>\n                    ), affecting transcription factor binding involved in B\u2010cell proliferation and differentiation, although it lacked association with immune markers. In conclusion, we confirm a genome\u2010wide significant association of the\n                    <jats:italic>ULK4<\/jats:italic>\n                    locus and MGUS risk, supporting its role in early B\u2010cell differentiation, and identify\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    as a candidate susceptibility locus warranting further investigation.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70427","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:21:20Z","timestamp":1773285680000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>ULK4<\/i>\n                    <\/scp>\n                    and\n                    <scp>\n                      <i>CDKN2A<\/i>\n                    <\/scp>\n                    polymorphisms influence the risk of developing monoclonal gammopathy of undetermined significance"],"prefix":"10.1002","author":[{"given":"Jos\u00e9 Manuel","family":"S\u00e1nchez\u2010Maldonado","sequence":"first","affiliation":[{"name":"Genomic Oncology Area GENYO, Centre for Genomics and Oncological Research: Pfizer\/University of Granada\/Andalusian Regional Government, PTS  Granada Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanataria IBs.Granada  Granada Spain"},{"name":"Genomic Epidemiology Group German Cancer Research Center (DKFZ)  Heidelberg Germany"}]},{"given":"Angelica","family":"Macauda","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Group German Cancer Research Center (DKFZ)  Heidelberg Germany"}]},{"given":"Antonio Jos\u00e9","family":"Cabrera\u2010Serrano","sequence":"additional","affiliation":[{"name":"Genomic Oncology Area GENYO, Centre for Genomics and Oncological Research: Pfizer\/University of Granada\/Andalusian Regional Government, PTS  Granada Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanataria IBs.Granada  Granada Spain"}]},{"given":"Hauke","family":"Thomsen","sequence":"additional","affiliation":[{"name":"MSB Medical School Berlin  Berlin Germany"}]},{"given":"Murat","family":"G\u00fcler","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Group German Cancer Research Center (DKFZ)  Heidelberg Germany"},{"name":"Medical Faculty Heidelberg University  Heidelberg Germany"}]},{"given":"Rob Ter","family":"Horst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences  Vienna Austria"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9692-101X","authenticated-orcid":false,"given":"Bethany","family":"van Guelpen","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Intervention, Oncology Unit Ume\u00e5 University  Ume\u00e5 Sweden"},{"name":"Wallenberg Centre for Molecular Medicine Ume\u00e5 University  Ume\u00e5 Sweden"}]},{"given":"Pavel","family":"Vodicka","sequence":"additional","affiliation":[{"name":"Department of the Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences  Prague Czech Republic"},{"name":"Biomedical Center, Faculty of Medicine in Pilsen Charles University  Pilsen Czech Republic"},{"name":"Institute of Biology and Medical Genetics, First Faculty of Medicine Charles University  Prague Czech Republic"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8364-6357","authenticated-orcid":false,"given":"Stefano","family":"Landi","sequence":"additional","affiliation":[{"name":"Department of Biology University of Pisa  Pisa Italy"}]},{"given":"Subhayan","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Division of Clinical Genetics, Department of Laboratory Medicine Lund University  Lund Sweden"}]},{"given":"Pelin","family":"\u00dcnal","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Group German Cancer Research Center (DKFZ)  Heidelberg Germany"}]},{"given":"Luc\u00eda","family":"Ruiz\u2010Dur\u00e1n","sequence":"additional","affiliation":[{"name":"Genomic Oncology Area GENYO, Centre for Genomics and Oncological Research: Pfizer\/University of Granada\/Andalusian Regional Government, PTS  Granada Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanataria IBs.Granada  Granada Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7874-3707","authenticated-orcid":false,"given":"Delphine","family":"Casabonne","sequence":"additional","affiliation":[{"name":"Unit of Infections and Cancer, Cancer Epidemiology Research Programme IDIBELL, Catalan Institute of Oncology  l'Hospitalet de Llobregat Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica Instituto de Salud Carlos III  Madrid Spain"}]},{"given":"Hartmut","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Heidelberg University  Heidelberg Germany"}]},{"given":"Istemi","family":"Serin","sequence":"additional","affiliation":[{"name":"Istanbul Basaksehir Cam and Sakura City Hospital, Department of Hematology and Adult Bone Marrow Transplantation Unit University of Health Sciences  Istanbul Turkey"}]},{"given":"Mar\u00eda","family":"Carretero\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Genomic Oncology Area GENYO, Centre for Genomics and Oncological Research: Pfizer\/University of Granada\/Andalusian Regional Government, PTS  Granada Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanataria IBs.Granada  Granada Spain"}]},{"given":"Elena","family":"Cabezudo","sequence":"additional","affiliation":[{"name":"Hematolog Catalan Institute of Oncology  l'Hospitalet de Llobregat Spain"},{"name":"Hospital de Sant Joan Desp\u00ed Mois\u00e8s Broggi  Sant Joan Desp\u00ed Spain"}]},{"given":"Fernando","family":"Reyes\u2010Zurita","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I University of Granada  Granada Spain"}]},{"given":"Aaron D.","family":"Norman","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Quantitative Health Sciences Mayo Clinic  Rochester Minnesota USA"}]},{"given":"Ram\u00f3n","family":"Garc\u00eda\u2010Sanz","sequence":"additional","affiliation":[{"name":"CIBERONC, Institute of Cancer and Hematological Diseases Gregorio Mara\u00f1\u00f3n General  Madrid Spain"}]},{"given":"Gabriele","family":"Capurso","sequence":"additional","affiliation":[{"name":"Pancreato\u2010Biliary Endoscopy and Endosonography Division Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute  Milan Italy"},{"name":"\u201cVita\u2010Salute\u201d San Raffaele University  Milan Italy"}]},{"given":"Per","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn  Bonn Germany"},{"name":"Department of Biomedicine University of Basel  Basel Switzerland"}]},{"given":"Ulrika","family":"Pettersson\u2010Kymmer","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Department of Pharmacology and Clinical Neuroscience Umea University  Umea Sweden"}]},{"given":"Francisco","family":"Jim\u00e9nez\u2010Romera","sequence":"additional","affiliation":[{"name":"Genomic Oncology Area GENYO, Centre for Genomics and Oncological Research: Pfizer\/University of Granada\/Andalusian Regional Government, PTS  Granada Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanataria IBs.Granada  Granada Spain"}]},{"given":"S. Vincent","family":"Rajkumar","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine Mayo Clinic  Rochester Minnesota USA"}]},{"given":"Niels","family":"Weinhold","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine V University of Heidelberg  Heidelberg Germany"}]},{"given":"Ludmila","family":"Vodickova","sequence":"additional","affiliation":[{"name":"Department of the Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences  Prague Czech Republic"},{"name":"Biomedical Center, Faculty of Medicine in Pilsen Charles University  Pilsen Czech Republic"},{"name":"Institute of Biology and Medical Genetics, First Faculty of Medicine Charles University  Prague Czech Republic"}]},{"given":"Christian","family":"Langer","sequence":"additional","affiliation":[{"name":"Kempten Clinic  Kempten Germany"}]},{"given":"Angelika","family":"Stein","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Group German Cancer Research Center (DKFZ)  Heidelberg Germany"}]},{"given":"Abdulkadir","family":"Karismaz","sequence":"additional","affiliation":[{"name":"Department of Hematology University of Health Sciences, Istanbul Training and Research Hospital  Istanbul Turkey"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2818-5487","authenticated-orcid":false,"given":"Victor","family":"Moreno","sequence":"additional","affiliation":[{"name":"Oncology Data Analytics Program Catalan Institute of Oncology (ICO), Hospitalet de Llobregat  Barcelona Spain"},{"name":"Colorectal Cancer Group ONCOBELL, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat  Barcelona Spain"},{"name":"Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP)  Madrid Spain"},{"name":"Department of Clinical Sciences, Faculty of Medicine and health Sciences and Universitat de Barcelona Institute of Complex Systems (UBICS) University of Barcelona  Barcelona Spain"}]},{"given":"Markus M.","family":"N\u00f6then","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn  Bonn Germany"}]},{"given":"Karl\u2010Heinz","family":"J\u00f6ckel","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen University of Duisburg\u2010Essen  Essen Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8831-7349","authenticated-orcid":false,"given":"Francesca","family":"Tavano","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d  San Giovanni Rotondo (FG) Italy"}]},{"given":"Joaqu\u00edn","family":"Mart\u00ednez\u2010L\u00f3pez","sequence":"additional","affiliation":[{"name":"Hospital Universitario 12 de Octubre University Complutense, CIBER\u2010ONC CB16\/12\/00369, CNIO  Madrid Spain"}]},{"given":"Shaji K.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine Mayo Clinic  Rochester Minnesota USA"}]},{"given":"Juan Francisco","family":"Guti\u00e9rrez\u2010Bautista","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanataria IBs.Granada  Granada Spain"},{"name":"Servicio de An\u00e1lisis Cl\u00ednicos e Inmunolog\u00eda University Hospital Virgen de las Nieves  Granada Spain"},{"name":"Departamento de Bioqu\u00edmica Biolog\u00eda Molecular e Inmunolog\u00eda III, University of Granada  Granada Spain"}]},{"given":"Daniela","family":"Basso","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Padova Medicina di Laboratorio  Padova Italy"}]},{"given":"Florentin","family":"Sp\u00e4th","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Intervention, Cancer Center, Hematology Ume\u00e5 University  Ume\u00e5 Sweden"}]},{"given":"Yolanda","family":"Benavente","sequence":"additional","affiliation":[{"name":"Unit of Infections and Cancer, Cancer Epidemiology Research Programme IDIBELL, Catalan Institute of Oncology  l'Hospitalet de Llobregat Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica Instituto de Salud Carlos III  Madrid Spain"},{"name":"Department of Public Health, Mental Health and Maternal and Child Health Nursing, Faculty of Nursing University of Barcelona  Barcelona Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-6872","authenticated-orcid":false,"given":"Michelle A. T.","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\u2014Myeloma, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center  Houston Texas USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6948-7273","authenticated-orcid":false,"given":"B\u00f6rge","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen University of Duisburg\u2010Essen  Essen Germany"}]},{"given":"Tereza","family":"Sevcikova","sequence":"additional","affiliation":[{"name":"Department of Hematooncology University Hospital Ostrava  Ostrava Czech Republic"},{"name":"Department of Hematooncology Faculty of Medicine University of Ostrava  Ostrava Czech Republic"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9639-7940","authenticated-orcid":false,"given":"Rui Manuel Vieira","family":"Reis","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Health Sciences University of Minho, Braga, Portugal and ICVS\/3B's\u2014PT Government Associate Laboratory  Braga\/Guimar\u00e3es Portugal"},{"name":"Molecular Oncology Research Center Barretos Cancer Hospital  Barretos Brazil"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Centre for Individualised Infection Medicine (CiiM) &amp; TWINCORE Joint Ventures between the Helmholtz\u2010Centre for Infection Research (HZI) and the Hannover Medical School (MHH)  Hannover Germany"}]},{"given":"Miguel \u00c1ngel","family":"L\u00f3pez\u2010Nevot","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanataria IBs.Granada  Granada Spain"},{"name":"Servicio de An\u00e1lisis Cl\u00ednicos e Inmunolog\u00eda University Hospital Virgen de las Nieves  Granada Spain"},{"name":"Departamento de Bioqu\u00edmica Biolog\u00eda Molecular e Inmunolog\u00eda III, University of Granada  Granada Spain"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Radboud Center for Infectious Diseases Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Department for Immunology &amp; Metabolism Life and Medical Sciences Institute (LIMES), University of Bonn  Bonn Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3220-9944","authenticated-orcid":false,"given":"Daniele","family":"Campa","sequence":"additional","affiliation":[{"name":"Department of Biology University of Pisa  Pisa Italy"}]},{"given":"Alyssa","family":"Clay\u2010Gilmour","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology Arnold School of Public Health, University of South Caroline  Greenville South Carolina USA"}]},{"given":"Susan L","family":"Slager","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics Department of Health Sciences Research  Rochester Minnesota USA"}]},{"given":"Kari","family":"Hemminki","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology German Cancer Research Center (DKFZ)  Heidelberg Germany"},{"name":"Faculty of Medicine and Biomedical Center in Pilsen Charles University in Prague  Pilsen Czech Republic"}]},{"given":"Celine M","family":"Vachon","sequence":"additional","affiliation":[{"name":"Hospital de Sant Joan Desp\u00ed Mois\u00e8s Broggi  Sant Joan Desp\u00ed Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9857-4728","authenticated-orcid":false,"given":"Asta","family":"F\u00f6rsti","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurooncology German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK)  Heidelberg Germany"},{"name":"Hopp Children's Cancer Center (KiTZ)  Heidelberg 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