ASSOCIATION OF GSTP1 AND ABCB1 POLYMORPHISMS WITH TOXICITY FROM FIRST-LINE CHEMOTHERAPY IN OVARIAN CARCINOMA

Background:The association of genes involved in detoxification and transport of platinum or taxanes with toxicity may impact an individual patients response to first-line chemotherapy for ovarian carcinoma. Aim: The aim of this study was to evaluate the association between genetic variation in GSTP1 and ABCB1 and toxicities in women with ovarian carcinoma. Methods: A cohort of 85 women with a confirmed histological diagnosis of ovarian carcinoma were prospectively recruited between January 2014 and April 2018. Polymorphisms in ABCB1 (rs11285O3, c.1236C > T; rs1O45642, c.3435C > T) and GSTP1 (rs1695, c.313A > G) were detected by realtime PCR and GSTM1 and GSTT1 were analyzed by the multiplex PCR and genetic deletions. The association between SNPs/deletions and toxicity (hematologic toxicities, nephrotoxicity and neurotoxicity) were evaluated by Fisher’s exact probability or Chi-square tests. Variants with p < .05 were included in logistic regression with clinical covariates. This study was approved by the local institutional ethics committee (CAAE: 578293.1.0000.5404). Results: Carriers of the ABCB1 c.3435C > T variant had increased risk of grade 3 and 4 anemia compared to non-carriers (OR 9.15, 95% confidence interval [CI]: 1.07-78.5, p = 0.043). In contrast, women heterozygous or homozygous for the GSTP1 c.313A > G variant had reduced risk of grade 3 and 4 anemia (OR 0.25, 95% CI: 0.69-0.921, p = 0.037). Carriers of the ABCB1 c.1236C > T polymorphism had increased risk of grade 2 and 3 neurotoxicity (OR 4.15, 95% CI: 1.33-12.95, c0.014). Conclusions: Polymorphisms in ABCB1 are associated with increased risk of developing anemia and neurotoxicity, possibly related to the role of the ABCB1 gene product P-glycoprotein in paclitaxel disposition. The GSTP1 c.313A > G variant could lead to reduced carboplatin exposure, which might decrease the risk of developing anemia in women with this polymorphism. Support: São Paulo Research Foundation (FAPESP) (no: 2016/22335-2) for funding for the conduction of the research.