Establishing a Familial Basis for Papillary Thyroid Carcinoma Using the Utah Population Database

IMPORTANCE Determining if relatives of patients diagnosed as having papillary thyroid carcinoma (PTC) are at increased risk of developing the same cancer-and if so, which relatives and to what degree-would help identify those who require closer clinical attention. This could lead to earlier cancer detection and improved prognoses. OBJECTIVE To define the familial risk of PTC using a unique population research database. DESIGN, SETTING, PARTICIPANTS Retrospective review at a tertiary care facility using the Utah Population Database, which is linked to medical records and the Utah Cancer Registry, from 1966 through 2011. The study population comprised 4460 patients diagnosed as having PTC in Utah between 1966 and 2011 and their first-through fifth-degree relatives and spouses. These patients were compared 5:1 with matched, population-based controls. MAIN OUTCOMES AND MEASURES Statistically significant increased risk of PTC in any first-through fifth-degree relatives or spouses of patients diagnosed as having this cancer. RESULTS First-, second-, and third-degree relatives of PTC probands had a significant increased risk of developing this cancer compared with population controls. First-degree relatives of probands were at a 5.4-fold increased risk (P < 10(-15)) of being diagnosed as having this cancer themselves. Second-and third-degree relatives had a 2.2-fold (P < 10(-11)) and 1.8-fold increased risk (P < 10(-8)), respectively. Siblings of probands were at highest risk (odd ratio, 6.8; P < 10(-15)). There was no significant increased risk observed in spouses of probands. CONCLUSIONS AND RELEVANCE In the largest population study to date, a high risk of PTC is confirmed in first-degree relatives. Furthermore, significant increased risk extends to second- and third-degree relatives but not to spouses of probands. Translational studies are needed to better define the genetic predisposition to familial papillary thyroid cancer and for the development and implementation of optimal screening approaches.