title: TP53 mutations in breast cancer tumors of patients from Rio de Janeiro, Brazil: association with risk factors and tumor characteristics.
abstract: Somatic mutations in the TP53 gene are the most frequently observed genetic alterations in human malignancies, including breast cancer, which is one of the leading causes of death among women in Brazil. In our study, we determined the frequency and the pattern of TP53 mutations in malignant breast tumors from 120 patients living in Rio de Janeiro, Brazil. TP53 mutations were found in 20% of the tumors, which contained a diversity of mutation types: missense (62.5%), nonsense (8.3%), silent (4.2%), intronic (12.5%), insertion (4.2%) and deletion (8.3%). Of a total of 15 missense mutations, 4 were observed at Arg248 and 2 at Cys242, which are directly involved in DNA binding and in zinc binding, respectively. A subgroup of 51 patients was analyzed with respect to the relation between the presence of TP53 mutations and classical risk factors and with tumor and patient characteristics. For this analysis, we used logistic regression and, in order to obtain more precise confidence intervals, they were recalculated using a bootstrap resampling technique. Our results demonstrate that these mutations are not statistically associated with the risk factors or the patients' characteristics. However, the presence of TP53 mutations is strongly associated with the aggressiveness of the tumors, measured by Elston classification (OR = 11.97 and 95% CI of 2.24-307.05). This finding is in agreement with previous studies, which report the presence of TP53 mutations in tumors with poor prognosis. This correlation between tumor aggressiveness and TP53 mutations could be a crucial variable for the treatment and prognosis of breast cancer.
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Brazil.
authors.forename: Tatiana A
authors.initials: TA
authors.lastname: Simão
authors.forename: Fabiana S
authors.initials: FS
authors.lastname: Ribeiro
authors.forename: Lídia M F
authors.initials: LM
authors.lastname: Amorim
authors.forename: Rodolpho M
authors.initials: RM
authors.lastname: Albano
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Andrada-Serpa
authors.forename: Lúis E B
authors.initials: LE
authors.lastname: Cardoso
authors.forename: Gulnar A S
authors.initials: GA
authors.lastname: Mendonça
authors.forename: Cláudia V
authors.initials: CV
authors.lastname: de Moura-Gallo
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D001938:Brazil / Q000453:epidemiology; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012907:Smoking; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53