O papel do polimorfismo do gene TP53 no códon 72 e sua relação com fatores de risco em mulheres brasileiras com câncer de mama
Ano de defesa: | 2016 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de São Paulo (UNIFESP)
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Programa de Pós-Graduação: |
Não Informado pela instituição
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Departamento: |
Não Informado pela instituição
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País: |
Não Informado pela instituição
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Palavras-chave em Português: | |
Link de acesso: | https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3636652 https://repositorio.unifesp.br/handle/11600/46360 |
Resumo: | We evaluated the association between TP53 gene polymorphisms and breast cancer in Brazilian women. Genomic DNA was extracted from oral smear cells collected from 659 women. TP53 gene polymorphism was investigated at codon Pro72Arg (CCC?CGC), using the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). TP53*72 presented the following genotypic distribution in patients from Amazônia-Ocidental: the control group was 26.42% homozygous Pro (Pro/Pro), 36.79% heterozygous (Arg/Pro), and 36.79% homozygous Arg (Arg/Arg). The genotypic distribution in breast cancer group was 15.53% homozygous Pro (Pro/Pro), 48.54% heterozygous (Arg/Pro), and 35,93% homozygous Arg (Arg/Arg) (odds ratio =1.952; 95% CI =0.983-3,876; p = 0.054). The risk factors ethnicity (p = 0.032), Progesterone Receptor (PR) (p = 0.022), HER-2 (p = 0.008) and molecular subtype (p =0,030) showed significance. The genotypic distribution in sample population from São Paulo (SP) and Amazônia-Ocidental in the control group was 20,9% homozygous Pro (Pro/Pro), 42,3% heterozygous (Arg/Pro), and 36.8% homozygous Arg (Arg/Arg). The genotypic distribution in breast cancer group was 15.4% homozygous Pro (Pro/Pro), 44.7% heterozygous (Arg/Pro), and 39.9% homozygous Arg (Arg/Arg) (odds ratio =1.449; 95% CI =0.941-2.231; p = 0.091). The features such as, age (p < 0,001), menarche (p < 0,001), pregnancy (p = 0,004), hormonal therapy (p = 0,021), ethnicity (p < 0,001) and state of origin (p < 0,001) were significant. We also evaluated the effect of the p53 - codon 72 - polymorphism on clinicopathologic features, Her-2 (p = 0,011) and the other variables did not showed significant differences. Our results compared the tumor aggressiveness in both groups? cases (SP and Amazônia-Ocidental) and presented in pregnancy, age at first term delivery, neoadjuvant chemotherapy, surgical treatment and lymph nodes committed significant differences. Hence, the TP53*72 polymorphism evaluated is associated with some risk factors and clinical variables. This SNP may be associated with prognosis due to its co-relation with breast cancer. |