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. H...
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crwiley:10.1002/cncr.32011 2024-09-15T18:26:11+00:00 Haploinsufficiency of UNC13D increases the risk of lymphoma Löfstedt, Alexandra Ahlm, Clas Tesi, Bianca Bergdahl, Ingvar A. Nordenskjöld, Magnus Bryceson, Yenan T. Henter, Jan‐Inge Meeths, Marie Cancerfonden Vetenskapsrådet Barncancerfonden Histiocytosis Association 2019 http://dx.doi.org/10.1002/cncr.32011 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcncr.32011 https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.32011 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cncr.32011 en eng Wiley http://creativecommons.org/licenses/by-nc/4.0/ Cancer volume 125, issue 11, page 1848-1854 ISSN 0008-543X 1097-0142 journal-article 2019 crwiley https://doi.org/10.1002/cncr.32011 2024-08-13T04:13:03Z 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 Wiley Online Library Cancer 125 11 1848 1854 |
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Wiley Online Library |
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crwiley |
language |
English |
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. |
author2 |
Cancerfonden Vetenskapsrådet Barncancerfonden Histiocytosis Association |
format |
Article in Journal/Newspaper |
author |
Löfstedt, Alexandra Ahlm, Clas Tesi, Bianca Bergdahl, Ingvar A. Nordenskjöld, Magnus Bryceson, Yenan T. Henter, Jan‐Inge Meeths, Marie |
spellingShingle |
Löfstedt, Alexandra Ahlm, Clas Tesi, Bianca Bergdahl, Ingvar A. Nordenskjöld, Magnus Bryceson, Yenan T. Henter, Jan‐Inge Meeths, Marie Haploinsufficiency of UNC13D increases the risk of lymphoma |
author_facet |
Löfstedt, Alexandra Ahlm, Clas Tesi, Bianca Bergdahl, Ingvar A. 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 |
Wiley |
publishDate |
2019 |
url |
http://dx.doi.org/10.1002/cncr.32011 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcncr.32011 https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.32011 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cncr.32011 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_source |
Cancer volume 125, issue 11, page 1848-1854 ISSN 0008-543X 1097-0142 |
op_rights |
http://creativecommons.org/licenses/by-nc/4.0/ |
op_doi |
https://doi.org/10.1002/cncr.32011 |
container_title |
Cancer |
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125 |
container_issue |
11 |
container_start_page |
1848 |
op_container_end_page |
1854 |
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1810466629663850496 |