Evaluating the Use of Tumor Bank DNA to Validate Genetic Factors Impacting Opioid Response in Patients with Advanced...

Opioids are first-line therapy for cancer pain, yet up to 30% of patients fail to achieve adequate control at standard doses. Opioid response is partly genetically mediated, and understanding these factors may improve symptom management. This project aimed to assess the feasibility of using tumor bank DNA for pharmacogenetic analyses and to validate previously identified genetic variants associated with opioid response using existing genetic and clinical data. In this retrospective cohort study, clinical data (morphine equivalent daily dose, demographics) and genetic data (single-nucleotide polymorphisms) were analyzed across 31 candidate loci. Adult deceased patients with melanoma, colorectal, or lung cancer treated with opioids between 2016 and 2021 and with available tumor bank DNA were included. Patients without sufficient DNA or not deceased were excluded. Of 3503 potential samples, 502 met the inclusion criteria. The median morphine equivalent daily dose was 40 mg (range 1-2140 mg). Eleven loci across six genes may be associated with higher (OPRM1, TAOK3, NFKBIA, COMT, and RHBDF2) and lower (COMT and GCH1) opioid dose requirements (p < 0.05, not significant after Bonferroni correction). Ultimately, tumor bank DNA is a feasible resource for pharmacogenetic research. Identified loci may contribute to variability in opioid response and support future personalized pain management strategies.