• J Pain Symptom Manage · Oct 2018

    Single-Nucleotide Polymorphisms in TAOK3 Are Associated With High Opioid Requirement for Pain Management in Patients With Advanced Cancer Admitted to a Tertiary Palliative Care Unit.

    • Timothy Gutteridge, Mahalakshmi Kumaran, Sunita Ghosh, Robin Fainsinger, Pål Klepstad, Yoko Tarumi, Sambasivarao Damaraju, and Vickie E Baracos.
    • University of Alberta Hospital, Edmonton, Alberta, Canada.
    • J Pain Symptom Manage. 2018 Oct 1; 56 (4): 560-566.

    PurposeDifferent amounts of opioid are required for the relief of cancer pain in different individuals, raising the possibility that genetic factors play a role. We tested the hypothesis that genetic variations in the TAOK3 (TAO kinase 3, encoding serine/threonine-protein kinase) explain some of the interindividual variations related to the morphine-equivalent daily dose (MEDD) in patients with cancer.Experimental DesignWe selected two single-nucleotide polymorphisms (SNPs) in the TAOK3, reported earlier to associate with higher MEDD in postoperative pain based on genome-wide association study. We investigated their association with MEDD in Canadian patients with cancer (n = 110) admitted to a tertiary palliative care unit. SNPs analyzed were rs1277441 (C/T, C = minor allele) and rs795484 (A/G, A = minor allele).ResultsMinor allele frequencies in our population were 0.29 (rs1277441) and 0.28 (rs795484). These SNPs were in perfect linkage disequilibrium (r2 = 0.97). SNPs in TAOK3 showed a significant association with mean MEDD ≥800 mg. For rs795484, MEDD values ≥800 mg occurred in patients who were GG (7%), GA (18%), and AA (57%) (P = 0.004; Fisher's exact test); similar results were obtained for rs1277441. Homozygous variants for either SNP had received higher numbers of different opioids (P = 0.021).ConclusionIn this cohort of patients with advanced cancer pain, TAOK3 SNPs were associated with opioid doses. This result supports the original findings from a GWAS in postoperative patients. The proportions of variant homozygotes (8.2% of patients) and their requirement for higher doses of opioids would appear potentially clinically important and should be validated in further studies.Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

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