Genotype and phenotype of patients with both familial adenomatous polyposis and thyroid carcinoma

The incidence of thyroid carcinoma in familial adenomatous polyposis (FAP) is thought to be 1%-2%, with the majority of cases being female. We have investigated the phenotype and genotype of 16 patients with FAP associated thyroid carcinoma. Among 1194 FAP patients studied in two high risk registries in North America (Familial Gastrointestinal Cancer Registry, Toronto and University California, San Francisco), 16 (1.3%) unrelated patients with FAP associated thyroid cancers were identified. Adenomatous polyposis coli (APC) gene testing was performed in 14 of the 16 cases. The average age of diagnosis for FAP and thyroid carcinoma was 29 years (range 17-52 years) and 33 years (range 17-55 years), respectively. All FAP patients except 1 had more than 100 colonic adenomas. Extracolonic manifestations, beside thyroid cancer, were presented in 81% (n = 13) of the patients, including gastric and duodenal polyps, desmoid tumor, osteoma, epidermoid cyst, sebaceous cyst and lipoma. Colorectal cancer was diagnosed in 38% (n = 6) of the patients. The pathology of the FAP associated thyroid cancer was predominantly papillary carcinoma. Germline mutations were identified in 12 of 14 patients tested. Mutations proximal to the mutation cluster region (1286-1513) were detected in 9 cases. Thyroid cancer in our FAP population was rare, predominantly in females and showed papillary carcinoma histology. Additionally, thyroid cancer in our patients occurred in the setting of classic FAP phenotype. Germline mutations were located predominantly outside the APC mutation cluster region.