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

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 and of the Association Francophone de Chirurgie Endocrinnienne cohort (>1600 patients included from the 1990s through 2024). Setting: Ambulatory and hospitalized care in referral centers. Patients: All men with a confirmed thymic tumor in the Groupe d'étude des Tumeurs Endocrines/Association Francophone de Chirurgie Endocrinnienne cohort were selected and matched to 2 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: Fifty-two 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). Conclusion: Men carrying nonsense MEN1 mutations may have an increased risk of thymic tumors and could benefit from enhanced thymic surveillance.