Clinical and genetic studies in familial nonmedullary thyroid cancer (FNMTC)

背景：甲状腺癌是美国增长最快的癌症诊断之一。非髓样甲状腺癌占所有甲状腺癌病例的95%。高达8%的非髓样甲状腺癌是遗传性的。家族性非髓样甲状腺癌(FNMTC)比散发性疾病更具侵袭性。目前尚未发现FNMTC的易感基因。筛查FNMTC高危家庭成员的最佳方法尚不清楚。该方案旨在确定FNMTC的自然病史和最佳筛查策略，并确定FNMTC的易感基因(S)。摘要：这是一项针对患有或有患非髓样甲状腺癌风险的个体的前瞻性研究。随着时间的推移，将在其家庭的背景下对个人进行研究，以便量化家庭成员患癌症的潜在风险，确定FNMTC的自然病史，确定家庭内的疾病谱，确定先兆状态，试图评估风险的遗传和环境因素的贡献，并制定有效的筛查战略。我们对筛查高危人群的中期分析显示，甲状腺结节和甲状腺癌的患病率远远高于一般人群，而且这些人患甲状腺肿瘤的年龄要年轻得多。从我们对家族性非髓样甲状腺癌家系的全外显子组测序研究的初步分析中，我们已经确定了候选易感基因，目前我们正在验证其他家族的易感基因，并进行功能基因组研究，以确定它们在肿瘤细胞生物学中的作用。

Background: Thyroid cancer is one of the fastest growing cancer diagnoses in the United States. Non-medullary thyroid cancer accounts for 95% of all thyroid cancer cases. Up to 8% of all non-medullary thyroid cancers are hereditary. Familial non-medullary thyroid cancer (FNMTC) is more aggressive than sporadic disease. No susceptibility gene for FNMTC has been identified. The best approach for screening at risk family members for FNMTC is unknown. This protocol is designed to determine the natural history and best screening strategy for FNMTC, and to identify susceptibility gene(s) for FNMTC. Summary: This is a prospective study of individuals with or at risk for non-medullary thyroid cancer. Individuals will be studied over time within the context of their families in order to quantify prospective risks of cancers in family members, to establish the natural history of FNMTC, define the spectrum of diseases within the families, to identify precursor states, to try to assess the contribution of genetic and environmental components of risk, and to develop effective screening strategies. Our interim analysis of screening at risk individuals shows that the prevalence of thyroid nodules and thyroid cancer is much higher than the general population and these individuals develop thyroid neoplasm at a much younger age. From our preliminary analysis of whole-exome sequencing studies in kindreds with familial non-medullary thyroid cancer, we have identified candidate susceptibility genes which we are currently validating in additional families and performing functional genomic studies to determine their role in tumor cell biology.