Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries
Authors: Vitale Antonio , Caggiano Valeria , Tufan Abdurrahman , Ragab Gaafar , Batu Ezgi Deniz , Portincasa Piero , Aragona Emma , Sota Jurgen , Conti Giovanni , De Paulis Amato , Rigante Donato , Olivieri Alma Nunzia , Şahin Ali , La Torre Francesco , Lopalco Giuseppe , Cattalini Marco , Maggio Maria Cristina , Insalaco Antonella , Sfikakis Petros P. , Verrecchia Elena , Yildirim Derya , Kucuk Hamit , Kardas Riza Can , Laymouna Ahmed Hatem , Ghanema Mahmoud , Saad Moustafa Ali , Sener Seher , Ercan Emreol Hulya , Ozen Seza , Jaber Nour , Khalil Mohamad , Di Ciaula Agostino , Gaggiano Carla , Malizia Giuseppe , Affronti Andrea , Patroniti Serena , Romeo Meri , Sbalchiero Jessica , Della Casa Francesca , Mormile Ilaria , Silvaroli Sara , Gicchino Maria Francesca , Çelik Neşe Çabuk , Tarsia Maria , Karamanakos Anastasios , Hernández-Rodríguez José , Parronchi Paola , Opris-Belinski Daniela , Barone Patrizia , Recke Andreas , Costi Stefania , Sfriso Paolo , Giardini Henrique A. Mayrink , Gentileschi Stefano , Wiesik-Szewczyk Ewa , Vasi Ibrahim , Loconte Roberta , Jahnz-Różyk Karina , Martín-Nares Eduardo , Torres-Ruiz Jiram , Cauli Alberto , Conforti Alessandro , Emmi Giacomo , Li Gobbi Francesca , Biasi Giovanni Rosario , Terribili Riccardo , Ruscitti Piero , Del Giudice Emanuela , Tharwat Samar , Brucato Antonio Luca , Ogunjimi Benson , Hinojosa-Azaola Andrea , Balistreri Alberto , Fabiani Claudia , Frediani Bruno , Cantarini Luca 
Published: May 2024

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.