CYP2D6 and CYP2E1 Gene Polymorphisms and Their Influence on Chemotherapy Treatment Outcome and Toxicity in Breast...

The majority of breast cancer cases are treated with invasive chemotherapy, which typically involves combinations of drugs as part of the standard therapeutic regimen. However, responses to chemotherapeutic agents and treatment outcomes can vary significantly among patients, and the occurrence of acute toxicity remains unpredictable. Phase I drug detoxification genes, such as those encoding cytochrome P450 enzymes, play a crucial role in the metabolism of chemotherapeutic drugs in cancer patients. Therefore, this study aimed to investigate polymorphisms in the CYP2D6 and CYP2E1 genes and their potential association with adverse reactions to doxorubicin and paclitaxel-based chemotherapy in breast cancer patients.

Genotyping of CYP2D6*3, CYP2D6*4, CYP2D6*10, CYP2D6*17, CYP2E1*5B, CYP2E1*6, CYP2E1*7B genes was performed among 200 breast cancer patients undergoing chemotherapy, using the  polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between gene polymorphisms and chemotherapy-induced toxicity was assessed using odds ratios (ORs) with 95% confidence intervals and corresponding p-values, where p ≤ 0.05 was considered statistically significant.

Following the analysis of CYP2D6 and CYP2E1 gene polymorphisms, we observed that CYP2D6*4 (rs3892097, G>A) (OR = 4.71; 95% CI: 1.93-11.46; p = 0.0006), CYP2D6*10 (rs1065852, C>T) (OR = 3.43; 95% CI: 1.43-8.21; p = 0.005), and CYP2E1*6 (rs6413432, T>A) (OR = 4.00; 95% CI: 1.66-9.61; p = 0.001) showed a positive association with severe peripheral neuropathy induced by paclitaxel-based chemotherapy in breast cancer patients. Additionally, CYP2E1*6 (rs6413432, T>A) (OR = 4.04; 95% CI: 1.72-9.50; p = 0.001) was significantly associated with paclitaxel-induced body ache in a subset of breast cancer patients.

The findings from this study conclude that polymorphisms in the CYP2D6 and CYP2E1 genes are associated with peripheral neuropathy, a non-hematological toxicity reaction, in breast cancer patients receiving paclitaxel-based chemotherapy.