Haploinsufficiency of UNC13D increases the risk of lymphoma
BACKGROUND: 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....
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Umeå universitet, Infektionssjukdomar
2019
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ftumeauniv:oai:DiVA.org:umu-157884 2023-10-09T21:54:36+02:00 Haploinsufficiency of UNC13D increases the risk of lymphoma Löfstedt, Alexandra Ahlm, Clas Tesi, Bianca Bergdahl, Ingvar Nordenskjöld, Magnus Bryceson, Yenan T. Henter, Jan-Inge Meeths, Marie 2019 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-157884 https://doi.org/10.1002/cncr.32011 eng eng Umeå universitet, Infektionssjukdomar Umeå universitet, Enheten för biobanksforskning Cancer, 0008-543X, 2019, 125:11, s. 1848-1854 orcid:0000-0003-1227-6859 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-157884 doi:10.1002/cncr.32011 PMID 30758854 ISI:000467473000015 Scopus 2-s2.0-85061503911 info:eu-repo/semantics/openAccess cancer hemophagocytic lymphohistiocytosis immune surveillance lymphocyte cytotoxicity lymphoma Cancer and Oncology Cancer och onkologi Article in journal info:eu-repo/semantics/article text 2019 ftumeauniv https://doi.org/10.1002/cncr.32011 2023-09-22T14:01:07Z BACKGROUND: 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' 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. METHODS: The authors exploited a founder effect of an UNC13D inversion, which abolishes Munc13-4 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 UNC13D mutation, all individuals with a diagnosis of lymphoma (487 patients) and matched controls (1844 controls) were assessed using polymerase chain reaction for carrier status. RESULTS: Among 487 individuals with lymphoma, 15 (3.1%) were heterozygous carriers of the UNC13D inversion, compared with 18 controls (1.0%) (odds ratio, 3.0; P = .002). It is interesting to note that a higher risk of lymphoma was attributed to female carriers (odds ratio, 3.7; P = .004). CONCLUSIONS: Establishing a high regional prevalence of the UNC13D 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-mediated surveillance of cancer. Furthermore, the results of the current study suggest that female carriers are more susceptible to lymphoma. Article in Journal/Newspaper Northern Sweden Umeå University: Publications (DiVA) Cancer 125 11 1848 1854 |
institution |
Open Polar |
collection |
Umeå University: Publications (DiVA) |
op_collection_id |
ftumeauniv |
language |
English |
topic |
cancer hemophagocytic lymphohistiocytosis immune surveillance lymphocyte cytotoxicity lymphoma Cancer and Oncology Cancer och onkologi |
spellingShingle |
cancer hemophagocytic lymphohistiocytosis immune surveillance lymphocyte cytotoxicity lymphoma Cancer and Oncology Cancer och onkologi Löfstedt, Alexandra Ahlm, Clas Tesi, Bianca Bergdahl, Ingvar Nordenskjöld, Magnus Bryceson, Yenan T. Henter, Jan-Inge Meeths, Marie Haploinsufficiency of UNC13D increases the risk of lymphoma |
topic_facet |
cancer hemophagocytic lymphohistiocytosis immune surveillance lymphocyte cytotoxicity lymphoma Cancer and Oncology Cancer och onkologi |
description |
BACKGROUND: 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' 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. METHODS: The authors exploited a founder effect of an UNC13D inversion, which abolishes Munc13-4 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 UNC13D mutation, all individuals with a diagnosis of lymphoma (487 patients) and matched controls (1844 controls) were assessed using polymerase chain reaction for carrier status. RESULTS: Among 487 individuals with lymphoma, 15 (3.1%) were heterozygous carriers of the UNC13D inversion, compared with 18 controls (1.0%) (odds ratio, 3.0; P = .002). It is interesting to note that a higher risk of lymphoma was attributed to female carriers (odds ratio, 3.7; P = .004). CONCLUSIONS: Establishing a high regional prevalence of the UNC13D 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-mediated surveillance of cancer. Furthermore, the results of the current study suggest that female carriers are more susceptible to lymphoma. |
format |
Article in Journal/Newspaper |
author |
Löfstedt, Alexandra Ahlm, Clas Tesi, Bianca Bergdahl, Ingvar Nordenskjöld, Magnus Bryceson, Yenan T. Henter, Jan-Inge Meeths, Marie |
author_facet |
Löfstedt, Alexandra Ahlm, Clas Tesi, Bianca Bergdahl, Ingvar Nordenskjöld, Magnus Bryceson, Yenan T. Henter, Jan-Inge Meeths, Marie |
author_sort |
Löfstedt, Alexandra |
title |
Haploinsufficiency of UNC13D increases the risk of lymphoma |
title_short |
Haploinsufficiency of UNC13D increases the risk of lymphoma |
title_full |
Haploinsufficiency of UNC13D increases the risk of lymphoma |
title_fullStr |
Haploinsufficiency of UNC13D increases the risk of lymphoma |
title_full_unstemmed |
Haploinsufficiency of UNC13D increases the risk of lymphoma |
title_sort |
haploinsufficiency of unc13d increases the risk of lymphoma |
publisher |
Umeå universitet, Infektionssjukdomar |
publishDate |
2019 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-157884 https://doi.org/10.1002/cncr.32011 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Cancer, 0008-543X, 2019, 125:11, s. 1848-1854 orcid:0000-0003-1227-6859 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-157884 doi:10.1002/cncr.32011 PMID 30758854 ISI:000467473000015 Scopus 2-s2.0-85061503911 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1002/cncr.32011 |
container_title |
Cancer |
container_volume |
125 |
container_issue |
11 |
container_start_page |
1848 |
op_container_end_page |
1854 |
_version_ |
1779318232933466112 |