GSTP1andABCB1Polymorphisms Predicting Toxicities and Clinical Management on Carboplatin and Paclitaxel‐Based Chemotherapy in Ovarian Cancer

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 ofGSTandABCB1genetic 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 ofGSTM1andGSTT1genes.GSTP1(c.313A>G/rs1695) andABCB1(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 theGSTP1c.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. TheGSTP1c.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). TheABCB1c.1236C>T was associated with increased risk of thrombocytopenia (OR: 0.15, 95% CI: 0.03–0.82,P = 0.03), whereasABCB1c.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 thatGSTP1c.313A>G,ABCB1c.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.