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Clin Transl Sci ; 14(2): 720-728, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33326171

RESUMO

Variation in drug disposition genes might contribute to susceptibility to toxicities and interindividual differences in clinical management on chemotherapy for epithelial ovarian cancer (EOC). This study was designed to explore the association of GST and ABCB1 genetic variation with hematologic and neurologic toxicity, changes in chemotherapy, and disease prognosis in Brazilian women with EOC. A total of 112 women with a confirmed histological diagnosis of EOC treated with carboplatin/paclitaxel were enrolled (2014-2019). The samples were analyzed by multiplex polymerase chain reaction (PCR) for the deletion of GSTM1 and GSTT1 genes. GSTP1 (c.313A>G/rs1695) and ABCB1 (c.1236C>T/rs1128503; c.3435C>T/rs1045642; c.2677G>T>A/rs2032582) single nucleotide polymorphisms (SNPs) were detected by real-time PCR. Subjects with the GSTP1 c.313A>G had reduced risk of anemia (odds ratio (OR): 0.17, 95% confidence interval (CI): 0.04-0.69, P = 0.01, dominant model) and for thrombocytopenia (OR: 0.27, 95% CI: 0.12-0.64, P < 0.01; OR 0.18, 95% CI 0.03-0.85, P = 0.03, either dominant or recessive model), respectively. The GSTP1 c.313A>G AG genotype was associated with a lower risk of dose delay (OR: 0.35, 95% CI: 0.13-0.90, P = 0.03). The ABCB1 c.1236C>T was associated with increased risk of thrombocytopenia (OR: 0.15, 95% CI: 0.03-0.82, P = 0.03), whereas ABCB1 c.3435C>T had increased risk of grade 2 and 3 neurotoxicity (OR: 3.61, 95% CI: 1.08-121.01, P = 0.03) in recessive model (CC + CT vs. TT). This study suggests that GSTP1 c.313A>G, ABCB1 c.1236C>T, and c.3435C>T SNP detection is a potential predictor of hematological toxicity and neurotoxicity and could help predict the clinical management of women with EOC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/terapia , Glutationa S-Transferase pi/genética , Neoplasias Ovarianas/terapia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carboplatina/farmacocinética , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/mortalidade , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Feminino , Seguimentos , Glutationa S-Transferase pi/metabolismo , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Ovariectomia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/farmacocinética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Intervalo Livre de Progressão , Adulto Jovem
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