{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:18:49Z","timestamp":1780924729720,"version":"3.54.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:p>Genetic variability in humans is influenced by many factors, such as natural selection, mutations, genetic drift, and migrations. Molecular epidemiology evaluates the contribution of genetic risk factors in the etiology, diagnosis, and prevention of a particular disease. Few areas of medicine have been so clearly affected by genetic diagnosis and management as multiple neoplasia type 2 (MEN2), in which activating pathogenic variants in the <jats:italic>RET<\/jats:italic> gene results in the development of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism in nearly 98, 50, and 25% of gene carriers, respectively. Here, we aimed to collect RET genotyping data worldwide to analyze the distribution and frequency of <jats:italic>RET<\/jats:italic> variants from a global perspective. We show that the mutational spectrum of <jats:italic>RET<\/jats:italic> is observed worldwide. The codon 634 variants seem to be the most prevalent, but there are differences in the type of amino acid exchanges among countries and in the frequencies of the other <jats:italic>RET<\/jats:italic> codon variants. Most interestingly, studies using haplotype analysis or pedigree linkage have demonstrated that some pathogenic <jats:italic>RET<\/jats:italic> variants have been transmitted to offspring for centuries, explaining some local prevalence due to a founder effect. Unfortunately, after almost three decades after the causative role of the germline <jats:italic>RET<\/jats:italic> variants has been reported in hereditary MTC, comprehensive genotyping data remain limited to a few countries. The heterogeneity of <jats:italic>RET<\/jats:italic> variants justifies the need for a global effort to describe epidemiological data of families with MEN2 to further understand the genetic background and environmental circumstances that affect disease presentation.<\/jats:p>","DOI":"10.1530\/eje-21-0753","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T17:43:48Z","timestamp":1636566228000},"page":"R15-R30","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":23,"title":["GLOBAL ENDOCRINOLOGY: Geographical variation in the profile of RET variants in patients with medullary thyroid cancer: a comprehensive review"],"prefix":"10.1093","volume":"186","author":[{"given":"Rui M B","family":"Maciel","sequence":"first","affiliation":[{"name":"1Laboratory of Molecular and Translational Endocrinology, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-5532","authenticated-orcid":true,"given":"Ana Luiza","family":"Maia","sequence":"additional","affiliation":[{"name":"2Thyroid Unit, Hospital de Cl\u00ednicas de Porto Alegre, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/186\/1\/EJE-21-0753.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/186\/1\/EJE-21-0753.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:17:05Z","timestamp":1676391425000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/186\/1\/R15\/6853010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,1]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/eje-21-0753","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,1]]}}}