TP53 p.Arg337His germline mutation prevalence in Southern Brazil: Further evidence for mutation testing in young breast cancer patients

PLoS One. 2018 Dec 31;13(12):e0209934. doi: 10.1371/journal.pone.0209934. eCollection 2018.

Abstract

Premenopausal breast cancer (BC) is a core tumor of Li-Fraumeni (LFS) and Li-Fraumeni-like (LFL) Syndromes, predisposition disorders caused by germline mutations in TP53 gene. In the Southern and Southeastern regions of Brazil, a specific TP53 germline mutation, c.1010G>A (p.Arg337His), was identified at a population frequency of 0.3%, the highest value ever described for a TP53 germline variation. In Brazilian BC patients, carrier frequency can vary from 0.5% to 8.7%. The current study assessed carrier frequency by genotyping TP53 c.1010G>A in 2 BC groups: 1) 315 patients unselected for age of diagnosis and family history (FH) and 2) 239 patients diagnosed before 46 years and without Chompret criteria for LFS or LFL. One carrier was identified in group 1 (0.3%; CI 95% 0.1-1.76%) and six carriers in group 2 (2.5%; CI 95% 0.93-5.39%). The frequencies differed significantly between groups (p = 0.04). The mutation carrier frequency observed in group 2 could justify mutation testing in BC patients diagnosed before 46 years and without Chompret criteria for LFS or LFL. Further studies in larger samples of BC patients of different ages and regions of the country are necessary to provide more definitive TP53 p.Arg337His carrier frequencies in different scenarios.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Amino Acid Substitution
  • Brazil / epidemiology
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Female
  • Genotype*
  • Germ-Line Mutation*
  • Humans
  • Middle Aged
  • Mutation, Missense*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53

Grants and funding

The study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil, grant number 308829/2013-1); Fundo de Incentivo a Pesquisa (FIPE, HCPA, Brazil, project numbers 2004-0438 and 2008-0022), and Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS, Brazil, grant number 1188-2551/13- 8). Patricia Ashton-Prolla and Sandra Leistner Segal are researchers from CNPq (Brazil). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.