{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:58:48Z","timestamp":1784224728602,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T00:00:00Z","timestamp":1550016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["CAN 2016\/275"],"award-info":[{"award-number":["CAN 2016\/275"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2014-02811"],"award-info":[{"award-number":["2014-02811"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["521-2011-3897"],"award-info":[{"award-number":["521-2011-3897"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006313","name":"Barncancerfonden","doi-asserted-by":"publisher","award":["KF2013-0022"],"award-info":[{"award-number":["KF2013-0022"]}],"id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006313","name":"Barncancerfonden","doi-asserted-by":"publisher","award":["PR2015-0005"],"award-info":[{"award-number":["PR2015-0005"]}],"id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006313","name":"Barncancerfonden","doi-asserted-by":"publisher","award":["PR2015-0082"],"award-info":[{"award-number":["PR2015-0082"]}],"id":[{"id":"10.13039\/501100006313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002136","name":"Histiocytosis Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002136","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Experimental models have demonstrated that immune surveillance by cytotoxic lymphocytes can protect from spontaneous neoplasms and cancer. In humans, defective lymphocyte cytotoxicity is associated with the development of hemophagocytic lymphohistiocytosis, a hyperinflammatory syndrome. However, to the best of the authors\u2019 knowledge, the degree to which human lymphocyte cytotoxicity protects from cancer remains unclear. In the current study, the authors examined the risk of lymphoma attributable to haploinsufficiency in a gene required for lymphocyte cytotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The authors exploited a founder effect of an\n                      <jats:italic>UNC13D<\/jats:italic>\n                      inversion, which abolishes Munc13\u20104 expression and causes hemophagocytic lymphohistiocytosis in an autosomal recessive manner. Within 2 epidemiological screening programs in northern Sweden, an area demonstrating a founder effect of this specific\n                      <jats:italic>UNC13D<\/jats:italic>\n                      mutation, all individuals with a diagnosis of lymphoma (487 patients) and matched controls (1844 controls) were assessed using polymerase chain reaction for carrier status\n                      <jats:italic>.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 487 individuals with lymphoma, 15 (3.1%) were heterozygous carriers of the\n                      <jats:italic>UNC13D<\/jats:italic>\n                      inversion, compared with 18 controls (1.0%) (odds ratio, 3.0;\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\u00a0.002). It is interesting to note that a higher risk of lymphoma was attributed to female carriers (odds ratio, 3.7;\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\u00a0.004).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Establishing a high regional prevalence of the\n                      <jats:italic>UNC13D<\/jats:italic>\n                      inversion, the authors have reported an overrepresentation of this mutation in individuals with lymphoma. Therefore, the results of the current study indicate that haploinsufficiency of a gene required for lymphocyte cytotoxicity can predispose patients to lymphoma, suggesting the importance of cytotoxic lymphocyte\u2010mediated surveillance of cancer. Furthermore, the results of the current study suggest that female carriers are more susceptible to lymphoma.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.32011","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T11:49:49Z","timestamp":1550058589000},"page":"1848-1854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Haploinsufficiency of\n                    <i>UNC13D<\/i>\n                    increases the risk of lymphoma"],"prefix":"10.1002","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1806-0768","authenticated-orcid":false,"given":"Alexandra","family":"L\u00f6fstedt","sequence":"first","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health Karolinska Institutet, Karolinska University Hospital Solna Stockholm Sweden"},{"name":"Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Center for Molecular Medicine Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clas","family":"Ahlm","sequence":"additional","affiliation":[{"name":"Infectious Diseases, Department of Clinical Microbiology Ume\u00e5 University Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Tesi","sequence":"additional","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health Karolinska Institutet, Karolinska University Hospital Solna Stockholm Sweden"},{"name":"Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Center for Molecular Medicine Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingvar A.","family":"Bergdahl","sequence":"additional","affiliation":[{"name":"Department of Biobank Research Ume\u00e5 University Ume\u00e5 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Nordenskj\u00f6ld","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Center for Molecular Medicine Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yenan T.","family":"Bryceson","sequence":"additional","affiliation":[{"name":"Center for Hematology and Regenerative Medicine, Department of Medicine Karolinska Institutet, Karolinska University Hospital Huddinge Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan\u2010Inge","family":"Henter","sequence":"additional","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health Karolinska Institutet, Karolinska University Hospital Solna Stockholm Sweden"},{"name":"Theme of Children\u2019s and Women\u2019s Health Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Meeths","sequence":"additional","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health Karolinska Institutet, Karolinska University Hospital Solna Stockholm Sweden"},{"name":"Clinical Genetics Unit, Department of Molecular Medicine and Surgery, Center for Molecular Medicine Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"},{"name":"Theme of Children\u2019s and Women\u2019s Health Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5022.779"},{"key":"e_1_2_8_3_1","volume-title":"Cellular and Humoral Aspects of the Hypersensitive States","author":"Lawrence HS","year":"1959"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1102-991"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101324"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.5.755"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031981"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809008106"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3245"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2014.03.014"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903815106"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-398958"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.073098"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25646"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-04-1477"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1179415"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000073"},{"key":"e_1_2_8_19_1","first-page":"697","article-title":"A single amino acid change A91V in perforin: a novel, frequent predisposing factor to childhood acute lymphoblastic leukemia?","volume":"90","author":"Santoro A","year":"2005","journal-title":"Haematologica"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"e536","DOI":"10.1016\/S2352-3026(15)00223-9","article-title":"Cancer risk in relatives of patients with a primary disorder of lymphocyte cytotoxicity: a retrospective cohort study","volume":"2","author":"L\u00f6fstedt A","journal-title":"Lancet Haematol"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404299"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.4161\/onci.24185"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-369090"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/14034950310001432"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3402\/gha.v5i0.19166"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25308"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0300"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-688960"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-573105"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2015.1"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-014-0439-2"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38793"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40438"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.121233"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.32011","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.32011","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.32011","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.32011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T04:47:12Z","timestamp":1761886032000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.32011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,13]]},"references-count":34,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1002\/cncr.32011"],"URL":"https:\/\/doi.org\/10.1002\/cncr.32011","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,13]]},"assertion":[{"value":"2018-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}