Importance: Li Fraumeni syndrome (LFS) is associated with a wide variety of tumors; nevertheless, thyroid carcinoma has not been evaluated in this syndrome. Due to the Brazilian founder mutation p.R337H, some tumors that have not been described in the classic LFS have been observed in a higher-than-expected prevalence in Brazil.
Objective: To determine the frequency of thyroid carcinoma in Brazilian carriers of a founder TP53 p.R337H mutation.
Design, setting, and participants: We reviewed medical records of patients with LFS with germline TP53 p.R337H mutation. For a better understanding of the correlation between thyroid carcinoma and LFS, tumor profile data of Brazilian carriers were analyzed. We included data from 193 patients with LFS with the TP53 p.R337H mutation from the database of the Department of Oncogenetics from the A.C. Camargo Cancer Center.
Main outcomes and measures: Thyroid tumors found in this population were reviewed with regard to age at diagnosis, sex, histologic subtype, and other tumors presented by these patients.
Results: Overall, 101 of 193 TP53 p.R337H mutation carriers with LFS from 58 families were cancer affected and, among them, thyroid carcinoma presented a prevalence of 10.9% (3 men and 8 women). The mean age at diagnosis was 44 years (median [SD], 43 [14.77] years). All the cases were histologically classified as papillary carcinomas, with 2 of them exhibiting follicular variant. The most common other cancers in the patients with thyroid carcinoma were breast cancer (5 patients) and soft-tissue sarcoma (2 patients).
Conclusions and relevance: Thyroid carcinoma may be associated with the Brazilian founder TP53 p.R337H mutation. Knowledge about this genotype/phenotype correlation is relevant to adjusting the LFS screening recommendations to these specific carriers.