VEXAS syndrome and cancer: Insights about a possible “Tip of the Iceberg”. Ambidirectional data from the international AIDA network registries
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an acquired autoinflammatory disorder characterized by severe chronic inflammation and an increased occurrence of hematologic neoplasms. Although chronic inflammation is a well-established risk factor for cancer, the specific contribution of UBA1 gene mutations to tumorigenesis remains unclear. Therefore, this study aimed to evaluate the overall cancer risk in patients with VEXAS syndrome, including both hematologic and non-hematologic neoplasms. METHODS: The relative risk (RR) of cancer was compared between VEXAS patients and a control cohort comprising individuals with Still's disease, Behçet's disease, and Schnitzler's syndrome. Logistic regression analysis was performed to identify variables potentially associated with cancer development. Patient's data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registries for VEXAS syndrome, Still's disease, Behçet's disease, and Schnitzler's syndrome. RESULTS: Ninety-six VEXAS patients and 2181 controls were enrolled. To minimize selection bias, only subjects aged >60 years were included, yielding 90 and 174 individuals in the exposed and control groups, respectively. The overall RR for cancer in VEXAS patients was 1.93 (95 % Confidence Interval [C.I.] 1.03-3.60, p = 0.036). Logistic regression analysis identified associations between cancer development and relapsing polychondritis (RR = 2.67, 95 %C.I. 1.22-10.64, p = 0.01), the p.Met41Thr mutation (RR = 3.33, 95 %C.I. 1.29-17.33, p = 0.02), elevated serum erythrocyte sedimentation rate (RR = 1.02, 95 %C.I. 1.01-1.05 p = 0.01), and lactate dehydrogenase (RR = 1.02, 95 %C.I. 1.01-1.07 p = 0.04) levels outside of flares. CONCLUSIONS: VEXAS patients exhibit a significantly increased risk of both hematologic and non-hematologic malignancies compared with controls, particularly among those with RP, p.Met41Thr mutation, and persistent systemic inflammation.
Authors: Francesco Gavioli, Valeria Caggiano, Jessica Sbalchiero, Micol Frassi, Francesca Crisafulli, Ilaria Cavazzana, Andrea Hinojosa-Azaola, Eduardo Martín-Nares, Guillermo Arturo Guaracha-Basañez, Jiram Torres-Ruiz, Ewa Wiesik-Szewczyk, Paolo Sfriso, Samuele Rizzo, Marta Schermi, Sara Bindoli, José Hernández-Rodríguez, Verónica Gómez-Caverzaschi, Olga Araújo, Annachiara Alemanno, Henrique A Mayrink Giardini, Andrés González-García, Francesco Placido, Giuseppe Lopalco, Ombretta Viapiana, Abdurrahman Tufan, Busra Koksoy, Fatih Mulayim, Pravin Hissaria, Mark Beecher, Thomas Panayiaris, Amato De Paulis, Lorenzo Dagna, Alessandro Tomelleri, Corrado Campochiaro, Serena Bugatti, Alessandra Milanesi, Guillermo Ruiz-Irastorza, Adriana Soto-Peleteiro, Matteo Piga, Alberto Cauli, Alberto Floris, Fabrizio Conti, Chiara Cardamone, Ilaria Zorzenon, Paola Triggianese, Carmelo Gurnari, Rosetta Vitetta, Marcella Prete, Vito Racanelli, Francesca Silvan, Rosaria Talarico, Adrián Mayo-Juanatey, Juan José Alegre-Sancho, Alessandra Renieri, Monica Bocchia, Anna Sicuranza, Alberto Balistreri, Vincenzo Sorrentino, Elisa Frullanti, Bruno Frediani, Claudia Fabiani, Luca Cantarini, Antonio Vitale
Institutions: University of Siena, Azienda Ospedaliera Universitaria Senese, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, University of Padua, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, University of Bari Aldo Moro, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Gazi Hastanesi, Gazi University, South Australia Pathology, Royal Adelaide Hospital, University of Naples Federico II, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, University of Pavia, Policlinico San Matteo Fondazione, University of the Basque Country, BioCruces Health research Institute, University of Cagliari, Sapienza University of Rome, AOU San Giovanni di Dio e Ruggi d'Aragona, University of Rome Tor Vergata, Policlinico Tor Vergata, Cleveland Clinic, University of Trento, Ospedale Santa Chiara, University of Pisa, Hospital Universitario Doctor Peset
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,370
OpenAlex ID: W7125388936