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.
J Pain Symptom Manage
; 56(4): 560-566, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-30031856
ABSTRACT
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 interindividual variations related to the morphine-equivalent daily dose (MEDD) in patients with cancer. EXPERIMENTALDESIGN:
We 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).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 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cuidados Paliativos
/
Proteínas Serina-Treonina Quinases
/
Polimorfismo de Nucleotídeo Único
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Dor do Câncer
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Analgésicos Opioides
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Adult
/
Aged
/
Aged80
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Pain Symptom Manage
Assunto da revista:
NEUROLOGIA
/
PSICOFISIOLOGIA
/
TERAPEUTICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Canadá