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

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.

To identify the genetic factors associated with the development of thymic tumors in patients with MEN1.

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).

Ambulatory and hospitalized care in referral centers.

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.

Development of thymic tumor.

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).

Men carrying nonsense MEN1 mutations may have an increased risk of thymic tumors and could benefit from enhanced thymic surveillance.