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Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors
OBJECTIVE: The aim of this study was to investigate the prevalence of cancer and associating clinical, immunological, and genetic factors in a German cohort of patients with common variable immunodeficiency (CVID). METHODS: In this retrospective monocenter cohort study, we estimated the standardized...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8893227/ https://www.ncbi.nlm.nih.gov/pubmed/35250968 http://dx.doi.org/10.3389/fimmu.2022.742530 |
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author | Bruns, Luzia Panagiota, Victoria von Hardenberg, Sandra Schmidt, Gunnar Adriawan, Ignatius Ryan Sogka, Eleni Hirsch, Stefanie Ahrenstorf, Gerrit Witte, Torsten Schmidt, Reinhold Ernst Atschekzei, Faranaz Sogkas, Georgios |
author_facet | Bruns, Luzia Panagiota, Victoria von Hardenberg, Sandra Schmidt, Gunnar Adriawan, Ignatius Ryan Sogka, Eleni Hirsch, Stefanie Ahrenstorf, Gerrit Witte, Torsten Schmidt, Reinhold Ernst Atschekzei, Faranaz Sogkas, Georgios |
author_sort | Bruns, Luzia |
collection | PubMed |
description | OBJECTIVE: The aim of this study was to investigate the prevalence of cancer and associating clinical, immunological, and genetic factors in a German cohort of patients with common variable immunodeficiency (CVID). METHODS: In this retrospective monocenter cohort study, we estimated the standardized incidence ratio (SIR) for different forms of cancer diagnosed in CVID patients. Furthermore, we evaluated the likely association of infectious and non-infectious CVID-related phenotypes with the diagnosis of cancer by calculation of the odds ratio. The genetic background of CVID in patients with cancer was evaluated with sequential targeted next-generation sequencing (tNGS) and whole-exome sequencing (WES). Patients’ family history and WES data were evaluated for genetic predisposition to cancer. RESULTS: A total of 27/219 patients (12.3%) were diagnosed with at least one type of cancer. Most common types of cancer were gastric cancer (SIR: 16.5), non-melanoma skin cancer (NMSC) (SIR: 12.7), and non-Hodgkin lymphoma (NHL) (SIR: 12.2). Immune dysregulation manifesting as arthritis, atrophic gastritis, or interstitial lung disease (ILD) was associated with the diagnosis of cancer. Furthermore, diagnosis of NMSC associated with the diagnosis of an alternative type of cancer. Studied immunological parameters did not display any significant difference between patients with cancer and those without. tNGS and/or WES yielded a definite or likely genetic diagnosis in 11.1% of CVID patients with cancer. Based on identified variants in cancer-associated genes, the types of diagnosed cancers, and family history data, 14.3% of studied patients may have a likely genetic susceptibility to cancer, falling under a known hereditary cancer syndrome. CONCLUSIONS: Gastric cancer, NMSC, and NHL are the most frequent CVID-associated types of cancer. Manifestations of immune dysregulation, such as arthritis and ILD, were identified as risk factors of malignancy in CVID, whereas studied immunological parameters or the identification of a monogenic form of CVID appears to have a limited role in the evaluation of cancer risk in CVID. |
format | Online Article Text |
id | pubmed-8893227 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88932272022-03-04 Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors Bruns, Luzia Panagiota, Victoria von Hardenberg, Sandra Schmidt, Gunnar Adriawan, Ignatius Ryan Sogka, Eleni Hirsch, Stefanie Ahrenstorf, Gerrit Witte, Torsten Schmidt, Reinhold Ernst Atschekzei, Faranaz Sogkas, Georgios Front Immunol Immunology OBJECTIVE: The aim of this study was to investigate the prevalence of cancer and associating clinical, immunological, and genetic factors in a German cohort of patients with common variable immunodeficiency (CVID). METHODS: In this retrospective monocenter cohort study, we estimated the standardized incidence ratio (SIR) for different forms of cancer diagnosed in CVID patients. Furthermore, we evaluated the likely association of infectious and non-infectious CVID-related phenotypes with the diagnosis of cancer by calculation of the odds ratio. The genetic background of CVID in patients with cancer was evaluated with sequential targeted next-generation sequencing (tNGS) and whole-exome sequencing (WES). Patients’ family history and WES data were evaluated for genetic predisposition to cancer. RESULTS: A total of 27/219 patients (12.3%) were diagnosed with at least one type of cancer. Most common types of cancer were gastric cancer (SIR: 16.5), non-melanoma skin cancer (NMSC) (SIR: 12.7), and non-Hodgkin lymphoma (NHL) (SIR: 12.2). Immune dysregulation manifesting as arthritis, atrophic gastritis, or interstitial lung disease (ILD) was associated with the diagnosis of cancer. Furthermore, diagnosis of NMSC associated with the diagnosis of an alternative type of cancer. Studied immunological parameters did not display any significant difference between patients with cancer and those without. tNGS and/or WES yielded a definite or likely genetic diagnosis in 11.1% of CVID patients with cancer. Based on identified variants in cancer-associated genes, the types of diagnosed cancers, and family history data, 14.3% of studied patients may have a likely genetic susceptibility to cancer, falling under a known hereditary cancer syndrome. CONCLUSIONS: Gastric cancer, NMSC, and NHL are the most frequent CVID-associated types of cancer. Manifestations of immune dysregulation, such as arthritis and ILD, were identified as risk factors of malignancy in CVID, whereas studied immunological parameters or the identification of a monogenic form of CVID appears to have a limited role in the evaluation of cancer risk in CVID. Frontiers Media S.A. 2022-02-17 /pmc/articles/PMC8893227/ /pubmed/35250968 http://dx.doi.org/10.3389/fimmu.2022.742530 Text en Copyright © 2022 Bruns, Panagiota, von Hardenberg, Schmidt, Adriawan, Sogka, Hirsch, Ahrenstorf, Witte, Schmidt, Atschekzei and Sogkas https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Bruns, Luzia Panagiota, Victoria von Hardenberg, Sandra Schmidt, Gunnar Adriawan, Ignatius Ryan Sogka, Eleni Hirsch, Stefanie Ahrenstorf, Gerrit Witte, Torsten Schmidt, Reinhold Ernst Atschekzei, Faranaz Sogkas, Georgios Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors |
title | Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors |
title_full | Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors |
title_fullStr | Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors |
title_full_unstemmed | Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors |
title_short | Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors |
title_sort | common variable immunodeficiency-associated cancers: the role of clinical phenotypes, immunological and genetic factors |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8893227/ https://www.ncbi.nlm.nih.gov/pubmed/35250968 http://dx.doi.org/10.3389/fimmu.2022.742530 |
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