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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

CYP Genotypes Are Associated with Toxicity and Survival in Osteosarcoma Patients

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Trujillo-Paolillo, Alini [1, 2] ; Salinas-Souza, Carolina [1] ; Dias-Oliveira, Indhira [1] ; Petrilli, Antonio S. [1, 3] ; Toledo, Silvia R. C. [1, 2]
Total Authors: 5
[1] Fed Univ Sao Paulo UNIFESP, EPM, Pediat Oncol Inst IOP, Support Grp Children & Adolescents Canc GRAACC, Rua Botucatu, 743, 8th Floor, BR-04023062 Sao Paulo - Brazil
[2] Fed Univ Sao Paulo UNIFESP, EPM, Discipline Hematol & Hemotherapy, Dept Clin & Expt Oncol, Sao Paulo - Brazil
[3] Fed Univ Sao Paulo UNIFESP, EPM, Discipline Pediat Oncol, Dept Pediat, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Web of Science Citations: 0

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)

FAPESP's process: 12/06421-5 - GSTM1, GSTT1, GSTM3, CYP1A2, CYP3A5 and CYP2C9 genes polymorphisms: validation of the role in chemotherapy response in a group of osteosarcoma patients
Grantee:Alini Trujillo Paolillo
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 11/10459-5 - Molecular e functional characterization of bone and soft tissue sarcomas of children and adolescents
Grantee:Silvia Regina Caminada de Toledo
Support Opportunities: Regular Research Grants