{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:10:01Z","timestamp":1788520201103,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006529","name":"Bundesamt f\u00fcr Strahlenschutz","doi-asserted-by":"publisher","award":["3622S32231"],"award-info":[{"award-number":["3622S32231"]}],"id":[{"id":"10.13039\/501100006529","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01KD2410A[EDI\u20104\u2010ALL]"],"award-info":[{"award-number":["01KD2410A[EDI\u20104\u2010ALL]"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70114736"],"award-info":[{"award-number":["70114736"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["495318549"],"award-info":[{"award-number":["495318549"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["496874193"],"award-info":[{"award-number":["496874193"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007311","name":"Deutsche Kinderkrebsstiftung","doi-asserted-by":"publisher","award":["A2023\/31"],"award-info":[{"award-number":["A2023\/31"]}],"id":[{"id":"10.13039\/501100007311","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2025,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Genetic predisposition is a major cause of cancer, yet little is known about the role of adult cancer predisposition syndromes (CPSs) in childhood cancers. Although extensively studied in adults, information about the impact of germline variants in genes associated with hereditary breast and ovarian cancer (HBOC) remains scarce in the pediatric context. To elucidate whether (likely) pathogenic variants (LP\/PVs) in 25 selected HBOC\u2010related genes may contribute to cancer risk in children, we analyzed the spectrum of occurring germline variants. We assessed 372 children (median age at diagnosis 5.1 [0\u201322.2] years; 160 girls [43%]), including 212 (57%) with hematologic neoplasms, 71 (19%) with brain tumors, and 89 (24%) with various solid entities. Twenty\u2010seven of 372 patients (7%) carried LP\/PVs in the candidate genes; for 12 of 27 (44%) no CPS was suspected prior to genotyping. LP\/PV carriers were particularly at risk for second malignancies (SMN; 5\/27 vs. 13\/345; OR\u2009=\u20095.8;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.0021); yet, LP\/PVs in SMN\u2010developing patients resided exclusively in\n                    <jats:italic>TP53<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093),\n                    <jats:italic>NBN<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091), and\n                    <jats:italic>ATM<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091). Burden testing of our single\u2010center cohort revealed considerable associations between monoallelic LP\/PVs in five HBOC\u2010related genes (\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>CHEK2<\/jats:italic>\n                    ,\n                    <jats:italic>ATM<\/jats:italic>\n                    ,\n                    <jats:italic>NF1<\/jats:italic>\n                    , and\n                    <jats:italic>NBN<\/jats:italic>\n                    ) and pediatric cancers compared to healthy adults (gnomAD v.3.1.1, non\u2010cancer dataset). Joint analyses adding 1120 individuals from a previous study Zhang et al. (2015) confirmed significant associations for\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>CHEK2<\/jats:italic>\n                    ,\n                    <jats:italic>NF1<\/jats:italic>\n                    ,\n                    <jats:italic>and MSH2<\/jats:italic>\n                    . Monoallelic LP\/PVs in constrained HBOC\u2010related genes are significantly associated with pediatric cancers. However, particularly in clinically unexpected cases, detection of contributing LP\/PVs by genotype\u2010driven approaches may improve patient outcomes by enabling risk\u2010adapted therapy and surveillance.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70097","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T15:19:13Z","timestamp":1756221553000},"page":"2447-2454","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Germline variants observed in pediatric cancer patients related to hereditary breast and ovarian cancer in adults"],"prefix":"10.1002","volume":"157","author":[{"given":"Katharina","family":"Daugs","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Brandes","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layal","family":"Yasin","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammarah","family":"Anwar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jubayer","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jil","family":"Bartrina y Manns","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Mescher","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-4737","authenticated-orcid":false,"given":"Arndt","family":"Borkhardt","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triantafyllia","family":"Brozou","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8206-9463","authenticated-orcid":false,"given":"Stefanie V.","family":"Junk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38142"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352\u20104642(20)30275\u20103"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.11.042"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201035727\u2010y"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404\u2010020\u201005883\u2010x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.05.055"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1508054"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25480"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201020\u20101631"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.72"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.5.9.3167"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689\u2010008\u20109195\u20107"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15061649"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102023\u2010177639"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14082000"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(16)30249\u20102"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431\u2010017\u20102997\u20106"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009231"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.54157"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201023\u20103683"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689\u2010021\u201000254\u20100"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201045975\u20109"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023023336"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djac151"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102308\u20107"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T08:55:32Z","timestamp":1761123332000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":25,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12,15]]}},"alternative-id":["10.1002\/ijc.70097"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70097","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]},"assertion":[{"value":"2024-09-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}