Year-end Sale % OFF 
Abstract
ObjectiveThe 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).MethodsIn 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.ResultsA 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.ConclusionsGastric 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.
Highlights
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency, comprising a heterogeneous group of disorders, which all associate with primary antibody production failure [1]
Notable monogenic primary immunodeficiency disorders (PIDs), whose genetic background directly predisposes to cancer, include the activated phosphoinositide 3-kinase d syndrome (APDS), nuclear factor kappa B subunit 1 (NF-kB1) insufficiency, and Signal transducer and activator of transcription 3 (STAT3) gainof-function syndrome [11–13]
The first diagnosis of cancer followed the diagnosis of CVID (20/27, 74.1%)
Summary
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency, comprising a heterogeneous group of disorders, which all associate with primary antibody production failure [1]. Non-infectious manifestations including autoimmunity, autoinflammation, and polyclonal lymphoproliferation can precede the onset of clinically evident immunodeficiency and dominate the phenotype of CVID [2]. Notable monogenic PIDs, whose genetic background directly predisposes to cancer, include the activated phosphoinositide 3-kinase d syndrome (APDS), nuclear factor kappa B subunit 1 (NF-kB1) insufficiency, and Signal transducer and activator of transcription 3 (STAT3) gainof-function syndrome [11–13]. Evidence for this stems from the detection of somatic mutations in PIK3CD, NFKB1, and STAT3 in human cancer genomes and the identification of their role in carcinogenesis [14–17]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
