{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:51:25Z","timestamp":1791244285728,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>MEN1, which is secondary to the mutation of the <jats:italic>MEN1<\/jats:italic> gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'\u00e9tude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (<jats:sc>s.e.m.<\/jats:sc>=0.13; <jats:italic>P<\/jats:italic>&lt;0.001) for pituitary tumor, 65% (<jats:sc>s.e.m.<\/jats:sc>=0.21; <jats:italic>P<\/jats:italic>&lt;0.001) for adrenal tumors, and 97% (<jats:sc>s.e.m.<\/jats:sc>=0.41; <jats:italic>P<\/jats:italic>=0.006) for thNETs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-15-0691","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T01:44:32Z","timestamp":1442886272000},"page":"819-826","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":36,"title":["Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'\u00e9tude des Tumeurs Endocrines 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