CYP450 Gene Polymorphisms and the Risk of Taxane-Induced Neurotoxicity in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

Background: Breast cancer (BC) is the most common cancer in women. Taxanes are widely used, but their neurotoxicity affects patients' quality of life. Genetic polymorphisms in CYP450 enzymes influence taxane metabolism, leading to variability in toxicity risk.

Methods: A literature search was conducted to identify studies on the association between CYP450 polymorphisms and Taxane-Induced Peripheral Neuropathy (TIPN) in BC patients. Odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) were estimated using a random-effects model in RStudio.

Results: Nine studies with 3034 patients were included. Overall CYP polymorphisms showed a significant association with TIPN (OR: 1.2877, 95% CI: 1.0262-1.6157). CYP1B1 polymorphism had an inconsistent link to TIPN by OR of 1.1524 (95% CI: 0.7441-1.7849). CYP2C8 polymorphism demonstrated the strongest association (OR: 1.5532, 95% CI: 1.2013-2.0082; HR: 1.5236, 95% CI: 1.1317-2.0512). CYP3A4 showed no significant association (OR: 1.0988, 95% CI: 0.5022-2.4404).

Conclusions: CYP2C8 polymorphisms were significantly linked to TIPN. While CYP1B1 showed inconsistent results, CYP3A4 had no significant association. These findings imply that CYP2C8 genetic variations may affect taxane metabolism and neurotoxicity risk, indicating that pharmacogenomic profiling could help personalize chemotherapy and reduce adverse effects.