Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, 90035-003, Porto Alegre, RS, Brazil; E-Mails:
Int J Mol Sci. 2012;13(1):221-39. doi: 10.3390/ijms13010221. Epub 2011 Dec 27.
Medullary thyroid carcinoma is a rare malignant tumor originating in parafollicular C cells. It accounts for 5 to 8% of all thyroid cancers. MTC develops in either sporadic (75%) or hereditary form (25%). Genetic and molecular studies have demonstrated the involvement of the RET proto-oncogene in hereditary MTC and, less often, in its sporadic form. Although a strong genotype-phenotype correlation has been described, wide clinical heterogeneity is observed among families with the same RET mutation or even in carriers of the same kindred. In recent years, several single nucleotide polymorphisms of the RET gene have been described in the general population as well as in patients with MTC. Some studies have reported associations between the presence of polymorphisms and development or progression of MTC. Nonetheless, other studies failed to demonstrate any effect of the RET variants. Differences in the genetic background of distinct populations or methodological approaches have been suggested as potential reasons for the conflicting results. Here, we review current knowledge concerning the molecular pathogenesis of sporadic and hereditary MTC. In particular, we analyze the role of RET polymorphisms in the clinical presentation and prognosis of MTC based on the current literature.
甲状腺髓样癌是一种起源于滤泡旁 C 细胞的罕见恶性肿瘤。它占所有甲状腺癌的 5%至 8%。MTC 以散发性（75%）或遗传性形式（25%）发生。遗传和分子研究表明，RET 原癌基因参与遗传性 MTC 的发生，在散发性 MTC 中也较少见。尽管已经描述了很强的基因型-表型相关性，但在具有相同 RET 突变的家族中甚至在相同家族的携带者中观察到广泛的临床异质性。近年来，在普通人群以及 MTC 患者中已经描述了几个 RET 基因的单核苷酸多态性。一些研究报告了多态性的存在与 MTC 的发生或进展之间的关联。然而，其他研究未能证明 RET 变异体的任何影响。不同人群的遗传背景或方法学方法的差异被认为是导致结果冲突的潜在原因。在这里，我们回顾了散发性和遗传性 MTC 的分子发病机制的现有知识。特别是，我们根据目前的文献分析了 RET 多态性在 MTC 的临床表现和预后中的作用。
