The Challenges of Estimating Medullary Thyroid Cancer Risk in Variant Carriers—Reevaluating RET
Menée à l'aide de données britaniques et américaines portant sur 506 544 personnes, cette étude analyse l'incidence du cancer médullaire de la thyroïde chez les individus porteurs de variants constitutionnels du gène RET en fonction de la présence d'une néoplasie endocrinienne multiple de type 2 (MEN2)
West et al have estimated the lifetime risk of medullary thyroid cancer among individuals with activating variants of the RET oncogene using 3 different patient cohorts. Multiple endocrine neoplasia type 2A (MEN2A) is a hereditary cancer syndrome characterized by medullary thyroid cancer and pheochromocytoma. In 1993, RET was discovered as the gene responsible for MEN2A. There are several recurrent variants that have been classified as either pathogenic or nonpathogenic. The majority of pathogenic variants are substitutions at a single nucleotide that change a single amino acid and activate the gene. Three common missense variants account for the majority of cases of medullary thyroid cancer. Unlike tumor suppressor genes, alterations that impair RET function (eg, protein-truncating variants) do not lead to disease. The authors set out to compare the incidence of medullary thyroid cancer in individuals with RET variants ascertained incidentally with individuals who attended a specialty genetics clinic.
JAMA Network Open , éditorial en libre accès, 2025