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

Abstract

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.

Influence of GSTP1 Polymorphism on the Clinical Outcomes of Patients With Advanced NSCLC Receiving First-Line Bevacizumab-Based Regimen: A Real-World Retrospective Study

“…In addition, located at coding area of GSTP1 gene, rs1695 polymorphism resulted in the alteration of amino acid from isoleucine to valine, which might compromise the expression and function of GSTP1 gene to some extent. 38 At present, the association between GSTP-1 gene expression level and prognosis of patients was still controversial. Previous study initiated by FM Yang and colleagues performed the research among patients with primary epithelial ovarian cancer (EOC) to investigate the prognostic significance of GSTP1 gene expression.…”

Influence of GSTP-1 Polymorphism on the Prognosis of Patients with High-Grade Glioma Who Received Temozolomide Plus Radiotherapy Adjuvant Treatment

“…Additionally, located at the coding area of GSTP-1 gene, 313A>G polymorphism resulted in the alteration of amino acid from Isoleucine to Valine, which could attenuate the expression and function of GSTP-1 gene to some extent. 35 At present, the association between GSTP-1 gene expression level and prognosis of patients is still controversial. Previously, Yang et al performed research among patients with primary epithelial ovarian cancer (EOC) to investigate the prognostic significance of GSTP-1 gene expression.…”

Análise de toxicidades relacionadas ao protocolo carboplatina e paclitaxel em pacientes com câncer de ovário

“…Em que pese os resultados promissores dessas estratégias, ainda não existe um algoritmo estruturado para prevenção de toxicidades para pacientes em uso do esquema CP na prática clínica. Ainda há muitos resultados clínicos inconclusivos sobre os fatores de risco envolvidos nas toxicidades, considerando tanto as variáveis individuais definidas (composição corporal, por exemplo) [33][34] quanto as indefinidas (polimorfismo genético) 14,[35][36] .…”

“…O uso desses medicamentos não é desprovido de riscos, uma vez que são capazes de provocar toxicidades hematológicas, neuropatias, fadiga, náuseas e outros eventos [12][13] . A ocorrência de toxicidades graves pode requerer redução da dose, atraso ou interrupção do tratamento, demandando intervenções clínicas e/ou comprometendo o prognóstico da doença 14 . Para prevenir a ocorrência ou minimizar a gravidade das toxicidades, o uso de medicamentos de suporte associado à combinação de QT é uma prática comum e recomendada 15 , especialmente para melhorar a qualidade de vida das mulheres em tratamento 1 .…”