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

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GUTTERIDGE, Timothy | KUMARAN, Mahalakshmi | GHOSH, Sunita | FAINSINGER, Robin L. | KLEPSTAD, Pål | TARUMI, Yoko | DAMARAJU, Sambasivarao | BARACOS, Vickie E.

PURPOSE: Different 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 inter-individual variations related to the morphine equivalent daily dose (MEDD) in cancer patients. EXPERIMENTAL DESIGN: We selected 2 single-nucleotide polymorphisms (SNPs) in the TAOK3, earlier reported to associate with higher MEDD in post-operative pain based on Genome-wide association study (GWAS). We investigated their association with MEDD in Canadian cancer patients (n=110) admitted to a tertiary palliative care unit (TPCU). SNPs analyzed were rs1277441 (C/T, C = minor allele) and rs795484 (A/G, A = minor allele). RESULTS: Minor 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). CONCLUSION: In this cohort of advanced cancer pain patients 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.

http://dx.doi.org/10.1016/j.jpainsymman.2018.07.011

Voir la revue «JOURNAL OF PAIN AND SYMPTOM MANAGEMENT, 56»

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