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

• Published in: PloS one Vol. 13; no. 12; p. e0209934
• Main Authors: Hahn, Eriza Cristina, Bittar, Camila Matzenbacher, Vianna, Fernanda Sales Luis, Netto, Cristina Brinckmann Oliveira, Biazús, Jorge Villanova, Cericatto, Rodrigo, Cavalheiro, José Antônio, de Melo, Márcia Portela, Menke, Carlos Henrique, Rabin, Eliane, Leistner-Segal, Sandra, Ashton-Prolla, Patricia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.12.2018; Public Library of Science (PLoS)
• Subjects: Adult; Age Factors; Amino Acid Substitution; Biology and Life Sciences; Brazil - epidemiology; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Cancer; Carrier frequencies; Cell cycle; Current carriers; Engineering and Technology; Female; Genes; Genetic counseling; Genetics; Genotype; Genotyping; Germ-Line Mutation; Humans; Internet; Medical diagnosis; Medicine and Health Sciences; Middle Aged; Mutation; Mutation, Missense; Ovarian cancer; p53 Protein; Patients; People and places; Population; Research and Analysis Methods; Tumor Suppressor Protein p53 - genetics; Tumors; Womens health; Brazil; Rio Grande do Sul Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0209934

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.