Correlation between chemotherapy-induced peripheral neuropathy severity and CYP3A4 variations in Rwandan cancer patients receiving paclitaxel treatment

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and distressing complication experienced by cancer patients undergoing paclitaxel therapy. This study investigates the correlation between CIPN severity and genetic variations in the CYP3A4 enzyme among Rwandan cancer patients receiving paclitaxel-based chemotherapy. A cohort of 90 patients, predominantly female (96.5%) with breast cancer (88.37%), was enrolled at Butaro Cancer Center; 86 completed all clinical visits. Patients were followed across four chemotherapy cycles, with neuropathic symptoms systematically assessed at each visit using standardized scoring tool, EORTC QLQ-CIPN20 scale tailored for CIPN severity. Blood samples were collected for genetic analysis, and CYP3A4 genotyping was conducted using Infinium Global screening Array, a robust and validated approach for single nucleotide polymorphism detection. Genotyping revealed that 67.4% carried the wild-type allele (AA), 27.9% were heterozygous mutants (AT), and 4.7% were homozygous mutants (TT) of CYP3A4. Longitudinal assessment of neuropathic symptoms over four visits demonstrated a significant increase in CIPN severity, particularly after the second chemotherapy cycle. Linear mixed-effects modeling showed a statistically significant effect of CYP3A4 genotype on CIPN severity(p<0.001), with homozygous mutants exhibiting markedly higher symptom scores compared to wild-type carriers (p<0.001). No significant difference was observed between heterozygous mutants and wild-type patients. These findings highlight a potential genetic predisposition contributing to CIPN severity and underscore the importance of incorporating CYP3A4 genotyping in clinical oncology practice. Early and systematic neuropathy monitoring is recommended to optimize paclitaxel treatment and improve patient quality of life. Further studies in diverse African populations are warranted to validate these results.