Genetic factors associated with thymic tumors in patients with MEN1: a nested case-control study in the GTE/AFCE cohort

Structured Abstract Context Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome characterized by tumors in multiple endocrine tissues. Its management is challenging because of its unpredictable course, particularly regarding thymic tumors, whose prognosis remains poor. Objective To identify the genetic factors associated with the development of thymic tumors in patients with MEN1. Design Nested case-control study in the Groupe d’étude des Tumeurs Endocrines (GTE) and of the Association Francophone de Chirurgie Endocrinnienne (AFCE) cohort (more than 1,600 patients included from the 1990s to 2024). Setting Ambulatory and hospitalized care in referral centers. Patients All men with a confirmed thymic tumor in the GTE/AFCE cohort were selected and matched to two nearest controls without thymic tumors, with a diagnosis of MEN1 identified at the same period (<1990; 1990-2000; ≥2000) and with an age at their last follow-up at least equal to the age of their paired case at the time of thymic tumor discovery. Main Outcome Measure Development of thymic tumor. Results 52 cases and 104 controls were included. Mean age at diagnosis of thymic tumor was 44 (SD=11). Nonsense mutations were associated with a higher risk of thymic tumors (OR=3.77, 95%-CI=1.36-10.50) than men with frameshift mutations. Among cases, the median age of onset of thymic tumor was almost identical between patients with a nonsense mutation and those without (43.8 vs. 43.2 years respectively). Conclusions Men carrying nonsense MEN1 mutations may have an increased risk of thymic tumors and could benefit from enhanced thymic surveillance.