TP53 p.R337H Germline Variant among Women at Risk of Hereditary Breast Cancer in a Public Health System of Midwest Brazil

Genes (Basel). 2024 Jul 16;15(7):928. doi: 10.3390/genes15070928.

Abstract

Despite the high prevalence of TP53 pathogenic variants (PV) carriers in the South and Southeast regions of Brazil, germline genetic testing for hereditary breast cancer (HBC) is not available in the Brazilian public health system, and the prevalence of Li-Fraumeni syndrome (LFS) is not well established in other regions of Brazil. We assessed the occurrence of TP53 p.R337H carriers among women treated for breast cancer (BC) between January 2021 and January 2022 at public hospitals of Brasilia, DF, Brazil. A total of 180 patients who met at least one of the NCCN criteria for HBC underwent germline testing; 44.4% performed out-of-pocket germline multigene panel testing, and 55.6% were tested for the p.R337H variant by allelic discrimination PCR. The median age at BC diagnosis was 43.5 years, 93% had invasive ductal carcinoma, 50% had estrogen receptor-positive/HER2 negative tumors, and 41% and 11% were diagnosed respectively at stage III and IV. Two patients (1.11%) harbored the p.R337H variant, and cascade family testing identified 20 additional carriers. The TP53 p.R337H detection rate was lower than that reported in other studies from south/southeast Brazil. Nonetheless, identifying TP53 PV carriers through genetic testing in the Brazilian public health system could guide cancer treatment and prevention.

Keywords: Li–Fraumeni syndrome; TP53 p.R337H; breast cancer; hereditary cancer.

MeSH terms

  • Adult
  • Aged
  • Brazil / epidemiology
  • Breast Neoplasms* / epidemiology
  • Breast Neoplasms* / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Testing / methods
  • Germ-Line Mutation*
  • Humans
  • Li-Fraumeni Syndrome / epidemiology
  • Li-Fraumeni Syndrome / genetics
  • Middle Aged
  • Public Health
  • Tumor Suppressor Protein p53* / genetics

Substances

  • Tumor Suppressor Protein p53
  • TP53 protein, human

Supplementary concepts

  • Breast Cancer, Familial

Grants and funding

The TaqMan® real-time PCR allelic discrimination assay kit was financed through Maria Isabel Achatz, who made them available with funding from a grant from Stand Up to Cancer (SU2C), 2018. The Instituto de Ensino e Pesquisa do Hospital Sirio-Libanes (IEP-HSL) financed the publication costs.