Association of OPRM1 and OPRD1 Polymorphisms with Pain and Opioid Adverse Reactions in Colorectal Cancer

<b>Background/Objectives</b>: Pain management in colorectal cancer is influenced by genetic variability in opioid receptor genes (<i>OPRM1</i> and <i>OPRD1</i>), potentially affecting opioid efficacy and adverse drug reactions (ADRs). This study evaluated the association of <i>OPRM1</i> (rs1799971 and rs510769) and <i>OPRD1</i> (rs2236861) polymorphisms with pain severity, opioid efficacy, and ADRs in Chilean colorectal cancer patients. <b>Methods</b>: The genotypes of <i>OPRM1</i> and <i>OPRD1</i> polymorphisms and clinical data from 69 colorectal cancer patients were analyzed. Associations between genotypes, ADRs, and pain severity (maximum Visual Analog Scale, VAS) were evaluated under inheritance models. <b>Results</b>: The <i>OPRM1</i> rs1799971 G allele was significantly associated with pain presence (<i>p</i> = 0.008), while <i>OPRD1</i> rs2236861 was linked to ADR risk (<i>p</i> = 0.042). Allelic distribution analysis revealed higher frequencies of the <i>OPRD1</i> G allele and <i>OPRM1</i> rs510769 T allele in patients with ADRs and pain, respectively. For <i>OPRM1</i> rs510769, the dominant model showed a significant association with pain severity (<i>p</i> = 0.033), while the overdominant model revealed a trend toward significance (<i>p</i> = 0.0504). Logistic regression model tests showed no significant predictive associations for the maximum VAS or ADRs under inheritance models. <b>Conclusions</b>: Genetic variations in <i>OPRM1</i> and <i>OPRD1</i> may play a role in pain perception and ADRs in colorectal cancer patients. These findings contribute to the understanding of pharmacogenomic factors in opioid therapy, emphasizing the need for further research to validate the clinical utility of these genetic markers.