Decoding the Impact of Genetic Polymorphisms in Xenobiotic Metabolizing Enzymes and Ovarian Cancer: A Comprehensive Review.

Ovarian cancer (OC), the third most common and fatal gynecological malignancy, is a heterogeneous disease characterized by genomic instability. The interaction between genetic and environmental factors, including xenobiotics, plays a crucial role in OC initiation, progression, and treatment resistance. Xenobiotic metabolism (XM) is a key process for metabolizing and detoxifying environmental carcinogens, drugs, and other xenobiotics. Variations in XM genes (XMGs), such as those encoding cytochrome P450s (CYPs), UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), N-acetyltransferases, and glutathione S-transferases (GSTs), can alter enzyme activity, thereby affecting detoxification, hormone metabolism, and clinical outcomes. Previous research has shown the effects of genetic variants on XM in OC, underscoring the importance of pharmacogenomics in tailoring personalized treatments. However, challenges persist, including individual variability, study inconsistencies, and insufficient ovarian-specific data on XM. This review provides a comprehensive overview of XM in OC. It emphasizes the importance of phase I and II enzymes in detoxification and biotransformation, and ABC transporters in drug metabolism and chemoresistance. This review provides insights into the emerging roles of CYPs, GSTs, glutathione peroxidases, myeloperoxidase, catalase, superoxide dismutase, SULTs, and UGTs, and addresses the need for further research to understand their influence on OC risk and prognosis. By addressing the gaps in ovarian-specific XM research, including their role in susceptibility and treatment response, these insights have the potential to advance targeted therapeutic strategies and overcome the challenges of chemoresistance in OC.