Genotypes Are Associated with Toxicity and Survival in Osteosarcoma Patients.

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 polymorphisms in osteosarcoma patients. The present study investigated DNA from peripheral blood from 70 osteosarcoma patients treated with high doses of cisplatin, doxorubicin, and methotrexate. (163C>A; rs762551); (1075A>C; rs1057910); and (6986A>G; rs776746) polymorphisms were investigated through real-time PCR using TaqMan probes. The allele did not present any association with clinical events. The CC/AC genotypes were associated with ototoxicity occurrence ( = 0.041, odds ratio [OR] = 8.4) and high grades of ototoxicity ( = 0.039, OR = 10.7), when compared with patients carrying the AA genotype. The CC genotype was associated with high grades of diarrhea ( = 0.043, OR = 4.6) and fever ( = 0.041, OR = 7.1) in comparison with the AA/AC genotypes. The CC genotype was associated with weight loss ( = 0.009, OR = 3.8) and high grades of hepatotoxicity ( = 0.010, OR = 4.3) when compared with the TT/CT genotypes. The CC/CT genotypes were associated with high grades of vomit ( = 0.013, OR = 10.8), pulmonary relapse absence ( = 0.029, OR = 9.5), and better overall and event-free survivals ( = 0.017, hazard ratio [HR] = 3.1;  = 0.044, HR = 2.5; respectively) when compared with the AA genotype. and alleles were associated with toxicity events. allele was associated with better survival. Thus, genotypes might be promising markers to tailoring treatment in osteosarcoma patients.