The Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism Is Associated with Oxycodone Requirements, Adverse Effects, and Pain Sensitivity in Cancer Patients

Abstract

Purpose. Catechol-O-methyltransferase (COMT) participates in the regulation of dopaminergic and adrenergic neurotransmission. COMT Val158Met polymorphism influences the efficacy and safety of opioids, but its association with oxycodone treatment in patients with cancer pain is yet to be elucidated. Hence, this study aimed to investigate the influence of COMT Val158Met polymorphism on oxycodone requirements, drug adverse effects, and pain sensitivity in patients with cancer. Methods. Patients with moderate to severe cancer pain treated with oxycodone were enrolled, of which 101 patients completed the study. All patients were genotyped for COMT Val158Met polymorphism using DNA from blood samples and were categorized into the wild-type group (n = 50) comprising individuals with the Val/Val genotype and the mutant group (n = 51) encompassing those with the Val/Met or Met/Met genotype. Numerical rating scale (NRS) scores, oxycodone requirements, and the incidence of oxycodone-related adverse drug reactions were compared between the two groups. Results. Patients in the mutant group exhibited higher NRS scores (6.18 ± 1.40) before the oxycodone treatment than those in the wild-type (5.48 ± 1.54) group (P = 0.017). Patients in the wild-type group required more oxycodone (96.00 ± 146.19 mg/24 h) than those in the mutant (77.25 ± 83.91 mg/24 h) group (P = 0.0365). The incidence rates of dysuria (2.0% vs. 16.0%, P = 0.016) and fatigue (0.0% vs. 12.0%, P = 0.013) were significantly lower in the mutant group than those in the wild-type group. Moreover, patients with at least one Met allele showed a lower risk of suffering from oxycodone-related side effects than those with the wild homozygote (41.2% vs. 68.0%, P = 0.007). Conclusion. Genetic variations in the COMT Val158Met gene may contribute to variability in the efficacy and safety of oxycodone in cancer pain treatment. The findings from this study emphasize the potential of pharmacogenetics in personalizing pain management. Furthermore, oxycodone therapeutic strategies can be designed based on genetic polymorphisms.