Frontiers in Immunology (May 2024)
Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries
- Antonio Vitale,
- Antonio Vitale,
- Valeria Caggiano,
- Valeria Caggiano,
- Abdurrahman Tufan,
- Gaafar Ragab,
- Gaafar Ragab,
- Ezgi Deniz Batu,
- Piero Portincasa,
- Emma Aragona,
- Jurgen Sota,
- Jurgen Sota,
- Giovanni Conti,
- Amato De Paulis,
- Amato De Paulis,
- Donato Rigante,
- Donato Rigante,
- Alma Nunzia Olivieri,
- Ali Şahin,
- Francesco La Torre,
- Giuseppe Lopalco,
- Marco Cattalini,
- Maria Cristina Maggio,
- Antonella Insalaco,
- Petros P. Sfikakis,
- Elena Verrecchia,
- Elena Verrecchia,
- Derya Yildirim,
- Hamit Kucuk,
- Riza Can Kardas,
- Ahmed Hatem Laymouna,
- Mahmoud Ghanema,
- Moustafa Ali Saad,
- Seher Sener,
- Hulya Ercan Emreol,
- Seza Ozen,
- Nour Jaber,
- Mohamad Khalil,
- Agostino Di Ciaula,
- Carla Gaggiano,
- Carla Gaggiano,
- Giuseppe Malizia,
- Andrea Affronti,
- Serena Patroniti,
- Meri Romeo,
- Jessica Sbalchiero,
- Jessica Sbalchiero,
- Francesca Della Casa,
- Ilaria Mormile,
- Sara Silvaroli,
- Maria Francesca Gicchino,
- Neşe Çabuk Çelik,
- Maria Tarsia,
- Maria Tarsia,
- Anastasios Karamanakos,
- José Hernández-Rodríguez,
- Paola Parronchi,
- Daniela Opris-Belinski,
- Patrizia Barone,
- Andreas Recke,
- Andreas Recke,
- Stefania Costi,
- Paolo Sfriso,
- Henrique A. Mayrink Giardini,
- Stefano Gentileschi,
- Stefano Gentileschi,
- Ewa Wiesik-Szewczyk,
- Ibrahim Vasi,
- Roberta Loconte,
- Karina Jahnz-Różyk,
- Eduardo Martín-Nares,
- Jiram Torres-Ruiz,
- Alberto Cauli,
- Alessandro Conforti,
- Giacomo Emmi,
- Giacomo Emmi,
- Francesca Li Gobbi,
- Giovanni Rosario Biasi,
- Giovanni Rosario Biasi,
- Riccardo Terribili,
- Riccardo Terribili,
- Piero Ruscitti,
- Emanuela Del Giudice,
- Samar Tharwat,
- Samar Tharwat,
- Antonio Luca Brucato,
- Benson Ogunjimi,
- Benson Ogunjimi,
- Benson Ogunjimi,
- Benson Ogunjimi,
- Andrea Hinojosa-Azaola,
- Alberto Balistreri,
- Claudia Fabiani,
- Claudia Fabiani,
- Bruno Frediani,
- Bruno Frediani,
- Luca Cantarini,
- Luca Cantarini
Affiliations
- Antonio Vitale
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, University of Siena, Siena, Italy
- Antonio Vitale
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Valeria Caggiano
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, University of Siena, Siena, Italy
- Valeria Caggiano
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Abdurrahman Tufan
- Gazi University Hospital, Department of Internal Medicine, Division of Rheumatology, Ankara, Türkiye
- Gaafar Ragab
- Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
- Gaafar Ragab
- Faculty of Medicine, Newgiza University, 6th of October City, Giza, Egypt
- Ezgi Deniz Batu
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University School of Medicine, Ankara, Türkiye
- Piero Portincasa
- Clinica Medica “A. Murri”, Division of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
- Emma Aragona
- Division of Gastroenterology, Ospedali Riuniti Villa Sofia-Vincenzo Cervello, Palermo, Italy
- Jurgen Sota
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, University of Siena, Siena, Italy
- Jurgen Sota
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Giovanni Conti
- Pediatric Nephrology and Rheumatology Unit, Azienda Ospedaliera Universitaria (AOU), “G. Martino”, Messina, Italy
- Amato De Paulis
- 0Department of Translational Medical Sciences, Section of Clinical Immunology, University of Naples Federico II, Naples, Italy
- Amato De Paulis
- 1Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Naples, Italy
- Donato Rigante
- 2Department of Life Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Donato Rigante
- 3Rare Diseases and Periodic Fevers Research Center, Università Cattolica del Sacro Cuore, Rome, Italy
- Alma Nunzia Olivieri
- 4Department of Woman, Child and of General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
- Ali Şahin
- 5Division of Rheumatology, Department of Internal Medicine, Sivas Cumhuriyet University Medical Faculty, Sivas, Türkiye
- Francesco La Torre
- 6Department of Pediatrics, Pediatric Rheumatology Center, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy
- Giuseppe Lopalco
- 7Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J) Policlinic Hospital, University of Bari, Bari, Italy
- Marco Cattalini
- 8Pediatrics Clinic, University of Brescia and Spedali Civili of Brescia, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Brescia, Italy
- Maria Cristina Maggio
- 9University Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE) “G. D’Alessandro”, University of Palermo, Palermo, Italy
- Antonella Insalaco
- 0Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, IRCCS [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Rome, Italy
- Petros P. Sfikakis
- 1Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens, [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Athens, Greece
- Elena Verrecchia
- 3Rare Diseases and Periodic Fevers Research Center, Università Cattolica del Sacro Cuore, Rome, Italy
- Elena Verrecchia
- 2Department of Aging, Neurological, Orthopedic and Head and Neck Sciences, Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
- Derya Yildirim
- Gazi University Hospital, Department of Internal Medicine, Division of Rheumatology, Ankara, Türkiye
- Hamit Kucuk
- Gazi University Hospital, Department of Internal Medicine, Division of Rheumatology, Ankara, Türkiye
- Riza Can Kardas
- Gazi University Hospital, Department of Internal Medicine, Division of Rheumatology, Ankara, Türkiye
- Ahmed Hatem Laymouna
- Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
- Mahmoud Ghanema
- Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
- Moustafa Ali Saad
- Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Giza, Egypt
- Seher Sener
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University School of Medicine, Ankara, Türkiye
- Hulya Ercan Emreol
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University School of Medicine, Ankara, Türkiye
- Seza Ozen
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University School of Medicine, Ankara, Türkiye
- Nour Jaber
- Clinica Medica “A. Murri”, Division of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
- Mohamad Khalil
- Clinica Medica “A. Murri”, Division of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
- Agostino Di Ciaula
- Clinica Medica “A. Murri”, Division of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Aldo Moro, Bari, Italy
- Carla Gaggiano
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, University of Siena, Siena, Italy
- Carla Gaggiano
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Giuseppe Malizia
- Division of Gastroenterology, Ospedali Riuniti Villa Sofia-Vincenzo Cervello, Palermo, Italy
- Andrea Affronti
- Division of Gastroenterology, Ospedali Riuniti Villa Sofia-Vincenzo Cervello, Palermo, Italy
- Serena Patroniti
- Pediatric Nephrology and Rheumatology Unit, Azienda Ospedaliera Universitaria (AOU), “G. Martino”, Messina, Italy
- Meri Romeo
- Pediatric Nephrology and Rheumatology Unit, Azienda Ospedaliera Universitaria (AOU), “G. Martino”, Messina, Italy
- Jessica Sbalchiero
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, University of Siena, Siena, Italy
- Jessica Sbalchiero
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Francesca Della Casa
- 0Department of Translational Medical Sciences, Section of Clinical Immunology, University of Naples Federico II, Naples, Italy
- Ilaria Mormile
- 0Department of Translational Medical Sciences, Section of Clinical Immunology, University of Naples Federico II, Naples, Italy
- Sara Silvaroli
- 3Department of Pediatric Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Maria Francesca Gicchino
- 4Department of Woman, Child and of General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
- Neşe Çabuk Çelik
- 5Division of Rheumatology, Department of Internal Medicine, Sivas Cumhuriyet University Medical Faculty, Sivas, Türkiye
- Maria Tarsia
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Maria Tarsia
- 4Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, Italy
- Anastasios Karamanakos
- 5Department of Rheumatology, “Evangelismos” General Hospital, Athens, Greece
- José Hernández-Rodríguez
- 6Department of Autoimmune Diseases, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic of Barcelona [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], University of Barcelona, Barcelona, Spain
- Paola Parronchi
- 7Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Daniela Opris-Belinski
- 8Rheumatology and Internal Medicine Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Patrizia Barone
- 9Pediatric Rheumatology Unit, Department of integrated Maternal-Child and Reproduction Activity AOU “Policlinico-San Marco”, Catania, Italy
- Andreas Recke
- 0Department of Dermatology, Allergology and Venerology, University Hospital Schleswig-Holstein, Lübeck, Germany
- Andreas Recke
- 1Autoinflammatory and Autoimmune Diseases (RITA) Center, European Reference Network (ERN) for Rare Immunodeficiency, Lübeck, Germany
- Stefania Costi
- 2Department of Clinical Sciences and Community Health, Research Center for Adult and Pediatric Rheumatic Diseases, University of Milan, Milan, Italy
- Paolo Sfriso
- 3Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy
- Henrique A. Mayrink Giardini
- 4Rheumatology Division, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, Brazil
- Stefano Gentileschi
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, University of Siena, Siena, Italy
- Stefano Gentileschi
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Ewa Wiesik-Szewczyk
- 5Department of Internal Medicine, Pneumonology, Allergology and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defense, Military Institute of Medicine, National Research Institute, Warsaw, Poland
- Ibrahim Vasi
- Gazi University Hospital, Department of Internal Medicine, Division of Rheumatology, Ankara, Türkiye
- Roberta Loconte
- 6Department of Pediatrics, Pediatric Rheumatology Center, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy
- Karina Jahnz-Różyk
- 5Department of Internal Medicine, Pneumonology, Allergology and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defense, Military Institute of Medicine, National Research Institute, Warsaw, Poland
- Eduardo Martín-Nares
- 6Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Jiram Torres-Ruiz
- 6Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Alberto Cauli
- 7Rheumatology Unit, Department of Medical Sciences, University and AOU of Cagliari, Cagliari, Italy
- Alessandro Conforti
- 8Ospedale San Paolo di Civitavecchia, U.O. Medicina Generale, ASL Roma 4, Civitavecchia, Rome, Italy
- Giacomo Emmi
- 9Department of Medical, Surgical and Health Sciences, University of Trieste, Italy, and Clinical Medicine and Rheumatology Unit, Cattinara University Hospital, Trieste, Italy
- Giacomo Emmi
- 0Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, VIC, Australia
- Francesca Li Gobbi
- 1Rheumatology Unit, Hospital S. Giovanni di Dio, Azienda USL-Toscana Centro, Florence, Italy
- Giovanni Rosario Biasi
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, University of Siena, Siena, Italy
- Giovanni Rosario Biasi
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Riccardo Terribili
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, University of Siena, Siena, Italy
- Riccardo Terribili
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Piero Ruscitti
- 2Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy
- Emanuela Del Giudice
- 3Pediatric and Neonatology Unit, Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Latina, Italy
- Samar Tharwat
- 4Rheumatology and Immunology Unit, Internal Medicine Department, Mansoura University, Mansoura, Egypt
- Samar Tharwat
- 5Department of Internal Medicine, Faculty of Medicine, Horus University, New Damietta, Egypt
- Antonio Luca Brucato
- 6Department of Biomedical and Clinical Sciences, Fatebenefratelli Hospital, Università di Milano, Milan, Italy
- Benson Ogunjimi
- 7Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium
- Benson Ogunjimi
- 8Antwerp Center for Translational Immunology and Virology, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Benson Ogunjimi
- 9Department of Pediatrics, Antwerp University Hospital, Antwerp, Belgium
- Benson Ogunjimi
- 0Center for Health Economics Research and Modeling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
- Andrea Hinojosa-Azaola
- 6Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Alberto Balistreri
- 1Bioengineering and Biomedical Data Science Lab, Department of Medical Biotechnologies, University of Siena, Siena, Italy
- Claudia Fabiani
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Claudia Fabiani
- 2Ophthalmology Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
- Bruno Frediani
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, University of Siena, Siena, Italy
- Bruno Frediani
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- Luca Cantarini
- Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, University of Siena, Siena, Italy
- Luca Cantarini
- Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy
- DOI
- https://doi.org/10.3389/fimmu.2024.1397890
- Journal volume & issue
-
Vol. 15
Abstract
ObjectiveInflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF.MethodsThe risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still’s disease patients and Behçet’s disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression.Results580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet’s disease patients and 497 Still’s disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still’s disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet’s disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (β1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (β1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (β1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (β1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (β1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (β1 = 2.089, 95% CI. 0.7-3.5, p=0.002).ConclusionsThe risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.
Keywords
