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. We have performed several genomic studies in tumor and germline DNA from familial and sporadic cases of non-medullary thyroid cancer. MicroRNA profiling of the sporadic and familial tumors matched for age and stage of cancer show distinctly different patterns of deregulated microRNA as compared to normal thyroid tissue. Also, we have found that cases of familial non-medullary thyroid cancer as compared to unaffected family members, sporadic thyroid cancer cases and healthy volunteer have short telomere length in germline DNA. We are currently determining if any of the telomere related protein may account for this difference, and are using a validation cohort of familial case of non-medullary thyroid cancer to confirm the presence of shorter telomere in familial non-medullary thyroid cancer as a risk factor.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Cancer Institute Division of Basic Sciences
Zip Code
Klubo-Gwiezdzinska, Joanna; Yang, Lily; Merkel, Roxanne et al. (2017) Results of Screening in Familial Non-Medullary Thyroid Cancer. Thyroid 27:1017-1024
Sadowski, Samira M; He, Mei; Gesuwan, Krisana et al. (2013) Prospective screening in familial nonmedullary thyroid cancer. Surgery 154:1194-8
Moses, Willieford; Weng, Julie; Kebebew, Electron (2011) Prevalence, clinicopathologic features, and somatic genetic mutation profile in familial versus sporadic nonmedullary thyroid cancer. Thyroid 21:367-71
Vriens, Menno R; Moses, Willieford; Weng, Julie et al. (2011) Clinical and molecular features of papillary thyroid cancer in adolescents and young adults. Cancer 117:259-67
Xiong, Yin; Zhang, Lisa; Holloway, Alisha K et al. (2011) MiR-886-3p regulates cell proliferation and migration, and is dysregulated in familial non-medullary thyroid cancer. PLoS One 6:e24717
Suh, Insoo; Filetti, Sebastiano; Vriens, Menno R et al. (2009) Distinct loci on chromosome 1q21 and 6q22 predispose to familial nonmedullary thyroid cancer: a SNP array-based linkage analysis of 38 families. Surgery 146:1073-80
Vriens, Menno R; Suh, Insoo; Moses, Willieford et al. (2009) Clinical features and genetic predisposition to hereditary nonmedullary thyroid cancer. Thyroid 19:1343-9