Autor(es)

Trujillo-Paolillo, Alini ; Salinas-Souza, Carolina ; Dias-Oliveira, Indhira ; Petrilli, Antonio S. ; Toledo, Silvia R. C.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY; v. 9, n. 6, p. 7-pg., 2020-04-16.

Resumo

Purpose: Osteosarcoma is the malignant bone tumor most common in children and adolescents. Many cytochrome P-450 (CYP) members detoxify anticancer drugs used in osteosarcoma treatment, and thus, the aim of the present study was to investigate CYP polymorphisms in osteosarcoma patients. Materials and Methods: The present study investigated DNA from peripheral blood from 70 osteosarcoma patients treated with high doses of cisplatin, doxorubicin, and methotrexate. CYP1A2*1F (163C>A; rs762551); CYP2C9*3 (1075A>C; rs1057910); and CYP3A5*3 (6986A>G; rs776746) polymorphisms were investigated through real-time PCR using TaqMan probes. Results: The CYP2C9*3 allele did not present any association with clinical events. The CYP1A2 CC/AC genotypes were associated with ototoxicity occurrence (p = 0.041, odds ratio [OR] = 8.4) and high grades of ototoxicity (p = 0.039, OR = 10.7), when compared with patients carrying the CYP1A2 AA genotype. The CYP1A2 CC genotype was associated with high grades of diarrhea (p = 0.043, OR = 4.6) and fever (p = 0.041, OR = 7.1) in comparison with the CYP1A2 AA/AC genotypes. The CYP3A5 CC genotype was associated with weight loss (p = 0.009, OR = 3.8) and high grades of hepatotoxicity (p = 0.010, OR = 4.3) when compared with the CYP3A5 TT/CT genotypes. The CYP3A5 CC/CT genotypes were associated with high grades of vomit (p = 0.013, OR = 10.8), pulmonary relapse absence (p = 0.029, OR = 9.5), and better overall and event-free survivals (p = 0.017, hazard ratio [HR] = 3.1; p = 0.044, HR = 2.5; respectively) when compared with the CYP3A5 AA genotype. Conclusion: CYP1A2*1A and CYP3A5*3 alleles were associated with toxicity events. CYP3A5*3 allele was associated with better survival. Thus, CYP genotypes might be promising markers to tailoring treatment in osteosarcoma patients. (AU)

• Processo FAPESP: 12/06421-5 - Validação do papel dos polimorfismos dos genes GSTM1, GSTT1, GSTM3, CYP1A2, CYP3A5 e CYP2C9 na resposta a quimioterapia em um grupo de pacientes com osteossarcoma
• Beneficiário: Alini Trujillo Paolillo
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 11/10459-5 - Caracterização molecular e funcional dos sarcomas ósseos e de partes moles da infância e da adolescência
• Beneficiário: Silvia Regina Caminada de Toledo
• Modalidade de apoio: Auxílio à Pesquisa - Regular