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 

TITLE=Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.742530

DOI=10.3389/fimmu.2022.742530

ISSN=1664-3224

ABSTRACT=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-associating phenotypes with the diagnosis of cancer by calculation of the odds ratio. The genetic background of CVID in patients with cancer was evaluated by means of targeted next-generation sequencing (tNGS). 
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 lymphomas (NHL) (SIR: 12.2). Immune dysregulation manifesting as arthritis, atrophic gastritis or interstitial lung disease (ILD), was associated with the diagnosis of cancer. Further, diagnosis of non-melanoma skin cancer 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. Finally, tNGS yielded a definite or likely genetic diagnosis in only 11.1% of CVID patients with cancer. 
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 appear to have a limited role in the evaluation of cancer risk in CVID.