{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:11:18Z","timestamp":1787008278476,"version":"build-2736575974"},"reference-count":31,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2020,11]]},"abstract":"\n Background:<\/jats:title>\n \n Sporadic medullary thyroid carcinoma (sMTC) is an uncommon neoplasia arising from the calcitonin-producing parafollicular cells of the thyroid. Previous studies evaluated whether single nucleotide polymorphisms (SNPs) within\n RET<\/jats:italic>\n (a pivotal proto-oncogene for this disease) are associated with the risk for developing sMTC, but the results are inconclusive.\n <\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n In this work, we evaluated the association of\n RET<\/jats:italic>\n -SNPs c.74-126G>T (rs2565206), p.Gly691Ser (rs1799939, G>A), p.Leu769\u2009=\u2009(rs1800861, G>T), p.Ser836\u2009=\u2009(rs1800862, C>T), and p.Ser904\u2009=\u2009(rs1800863, C>G) (listed in the order of their chromosomal location) with sMTC. This is one of the largest case\n \u2013<\/jats:bold>\n control association studies carried out on sMTC, including 585 sMTC cases (negative for germline mutations within\n RET<\/jats:italic>\n ), 1529 patients affected by sporadic nonmedullary thyroid carcinoma (sNMTC), and 989 healthy controls, from central and southern Italy and collected in the period 2000\u20132017.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n sNMTC patients showed similar genotype and allele frequencies compared with healthy controls. On the other hand, among sMTC patients, the T-allele of p.Leu769\u2009=\u2009was less frequent (OR\u2009=\u20090.70 [CI 0.58\u20130.84],\n p<\/jats:italic>\n \u2009=\u20091.9\u2009\u00d7\u200910\n \u22124<\/jats:sup>\n ) and rare homozygotes TT showed an OR\u2009=\u20090.32 ([CI 0.17\u20130.60],\n p<\/jats:italic>\n \u2009=\u20092.3\u2009\u00d7\u200910\n \u22124<\/jats:sup>\n ). Moreover, a statistically significant excess of the haplotype 2 (characterized by the alleles T-G-G-C-C of the listed SNPs) was observed (\n p<\/jats:italic>\n \u2009=\u20093.9\u2009\u00d7\u200910\n \u22123<\/jats:sup>\n ). The SNPs were not associated with the expression of\n RET<\/jats:italic>\n mRNA, that is, they did not exert an effect in\n cis<\/jats:italic>\n as quantitative trait locus (cis-eQTL). However, a strong eQTL association was found for p.Leu769\u2009=\u2009and the neighboring gene\n CSGALNACT2<\/jats:italic>\n (\n p<\/jats:italic>\n \u2009=\u20099.3\u2009\u00d7\u200910\n \u221250<\/jats:sup>\n ; effect-size\u2009=\u2009\u22120.65), whose function in cancer is unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n \n This study shows that specific\n RET<\/jats:italic>\n haplotypes, in particular haplotype 2 and the T-allele of p.Leu769\u2009=\u2009, are associated with a reduced risk of sMTC in Italians.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/thy.2019.0352","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T04:12:50Z","timestamp":1585627970000},"page":"1579-1588","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Polymorphisms Within the\n RET<\/i>\n Proto-Oncogene and Risk of Sporadic Medullary Thyroid Carcinoma"],"prefix":"10.1177","volume":"30","author":[{"given":"Federica","family":"Gemignani","sequence":"first","affiliation":[{"name":"Department of Biology, University of Pisa, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Romei","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Clinical and Experimental Medicine, University Hospital of Cisanello, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Ciampi","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Clinical and Experimental Medicine, University Hospital of Cisanello, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alda","family":"Corrado","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ombretta","family":"Melaiu","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisella","family":"Figlioli","sequence":"additional","affiliation":[{"name":"IFOM, The FIRC Institute of Molecular Oncology, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Bonotti","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, Hospital of Cisanello, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudy","family":"Foddis","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, Hospital of Cisanello, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Cristaudo","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, Hospital of Cisanello, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Operative Unit of Laboratory of Clinical Chemistry Analyses, University Hospital of Cisanello, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Vivaldi","sequence":"additional","affiliation":[{"name":"Operative Unit of Laboratory of Clinical Chemistry Analyses, University Hospital of Cisanello, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Cipollini","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Landi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Elisei","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Department of Clinical and Experimental Medicine, University Hospital of Cisanello, Pisa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2004.02037.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.11"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0335"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1998.00392.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.5603\/EP.2015.0018"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1921"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.10.5801"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2006-0017"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2009.02113.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.7.7678"},{"key":"e_1_3_3_12_2","first-page":"509","article-title":"Molecular 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Mol Cell Biol, 13:358\u2013366.","journal-title":"Mol Cell Biol"},{"key":"e_1_3_3_14_2","first-page":"198","article-title":"Detection of a novel type of RET rearrangement (PTC5) in thyroid carcinomas after Chernobyl and analysis of the involved RET-fused geneRFG5","volume":"58","author":"Klugbauer S","year":"1998","unstructured":"Klugbauer S, , Demidchik EP, , Lengfelder E, , Rabes HM. 1998. Detection of a novel type of RET rearrangement (PTC5) in thyroid carcinomas after Chernobyl and analysis of the involved RET-fused geneRFG5. 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Cancer Res, 60:2786\u20132789.","journal-title":"Cancer Res"},{"key":"e_1_3_3_16_2","first-page":"1093","article-title":"Molecular and biochemical analysis of RET\/PTC4, a novel oncogenic rearrangement between RET and ELE1 genes, in a post-Chernobyl papillary thyroid cancer","volume":"13","author":"Fugazzola L","year":"1996","unstructured":"Fugazzola L, , Pierotti MA, , Vigano E, , Pacini F, , Vorontsova TV, , Bongarzone I. 1996. Molecular and biochemical analysis of RET\/PTC4, a novel oncogenic rearrangement between RET and ELE1 genes, in a post-Chernobyl papillary thyroid cancer. Oncogene, 13:1093\u20131097.","journal-title":"Oncogene"},{"key":"e_1_3_3_17_2","first-page":"1690","article-title":"Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children","volume":"57","author":"Nikiforov YE","year":"1997","unstructured":"Nikiforov YE, , Rowland JM, , Bove KE, , Monforte-Munoz H, , Fagin JA. 1997. Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children. 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