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dc.contributor.authorBarratt, D.-
dc.contributor.authorKlepstad, P.-
dc.contributor.authorDale, O.-
dc.contributor.authorKaasa, S.-
dc.contributor.authorSomogyi, A.-
dc.contributor.editorGao, C.-
dc.identifier.citationPLoS One, 2015; 10(9):e0137179-1-e0137179-13-
dc.description.abstractCommon adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4), cognitive dysfunction (Mini-Mental State Examination ≤ 23), sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients.-
dc.description.statementofresponsibilityDaniel T. Barratt, Pål Klepstad, Ola Dale, Stein Kaasa, Andrew A. Somogyi-
dc.publisherPublic Library of Science-
dc.rights© 2015 Barratt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited-
dc.subjectAnalgesics, Opioid-
dc.subjectAdministration, Cutaneous-
dc.subjectKarnofsky Performance Status-
dc.subjectCognition Disorders-
dc.subjectPolymorphism, Single Nucleotide-
dc.subjectAged, 80 and over-
dc.subjectMiddle Aged-
dc.subjectMyeloid Differentiation Factor 88-
dc.subjectImmunity, Innate-
dc.subjectYoung Adult-
dc.subjectPain Management-
dc.titleInnate immune signalling genetics of pain, cognitive dysfunction and sickness symptoms in cancer pain patients treated with transdermal fentanyl-
dc.typeJournal article-
dc.identifier.orcidBarratt, D. [0000-0001-6261-353X]-
dc.identifier.orcidSomogyi, A. [0000-0003-4779-0380]-
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