{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:20:56Z","timestamp":1792804856642,"version":"4.5.0"},"reference-count":126,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.ejphar.2026.179173","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:55:18Z","timestamp":1784822118000},"page":"179173","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Role of genetic polymorphisms on opioid safety and efficacy in cancer pain: A systematic review and meta-analysis"],"prefix":"10.1016","volume":"1031","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1607-4728","authenticated-orcid":false,"given":"Mikail","family":"Akan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Panina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6153-2446","authenticated-orcid":false,"given":"Mikhail","family":"Khandokhin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6050-4708","authenticated-orcid":false,"given":"Salahuddin","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helgi B.","family":"Schi\u00f6th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Mwinyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2026.179173_bib1","series-title":"StatPearls","article-title":"Hydromorphone","author":"Abi-Aad","year":"2024"},{"key":"10.1016\/j.ejphar.2026.179173_bib2","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1097\/ALN.0b013e318238bba6","article-title":"Molecular mechanisms of opioid receptor-dependent signaling and behavior","volume":"115","author":"Al-Hasani","year":"2011","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2026.179173_bib3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00228-011-1093-5","article-title":"Do CYP2D6 genotypes reflect oxycodone requirements for cancer patients treated for cancer pain? A cross-sectional multicentre study","volume":"68","author":"Andreassen","year":"2012","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"10.1016\/j.ejphar.2026.179173_bib4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0137179","article-title":"Innate immune signalling genetics of pain, cognitive dysfunction and sickness symptoms in cancer pain patients treated with transdermal fentanyl","volume":"10","author":"Barratt","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.ejphar.2026.179173_bib6","doi-asserted-by":"crossref","first-page":"S59","DOI":"10.33549\/physiolres.934325","article-title":"Epidural analgesia with sufentanil in relation to OPRM1 and ABCB1 polymorphisms","volume":"68","author":"Barto\u0161ov\u00e1","year":"2019","journal-title":"Physiol. Res."},{"key":"10.1016\/j.ejphar.2026.179173_bib5","author":"Bartosova"},{"key":"10.1016\/j.ejphar.2026.179173_bib7","author":"Bastami"},{"key":"10.1016\/j.ejphar.2026.179173_bib8","article-title":"Tramadol, pharmacology, side effects, and Serotonin syndrome","author":"Beakley","year":"2015","journal-title":"A Review - PubMed"},{"key":"10.1016\/j.ejphar.2026.179173_bib9","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2019.37.15_suppl.e23133","article-title":"Genetic variability of tramadol pharmacokinetic genes and pain treatment outcome after breast cancer surgery","volume":"37","author":"Besic","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejphar.2026.179173_bib10","doi-asserted-by":"crossref","DOI":"10.15275\/rusomj.2020.0417","article-title":"Predicting opioid therapy safety in pancreatic cancer patients","volume":"9","author":"Bobrova","year":"2020","journal-title":"Russ. Open Med. J."},{"key":"10.1016\/j.ejphar.2026.179173_bib11","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/cpt.771","article-title":"Analgesic plasma concentrations of oxycodone after surgery for breast cancer-which factors matter?","volume":"103","author":"Cajanus","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.ejphar.2026.179173_bib12","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/sj.clpt.6100385","article-title":"Association of ABCB1\/MDR1 and OPRM1 gene polymorphisms with morphine pain relief","volume":"83","author":"Campa","year":"2008","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.ejphar.2026.179173_bib13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0304-3959(99)00073-1","article-title":"An international survey of cancer pain characteristics and syndromes","volume":"82","author":"Caraceni","year":"1999","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib14","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.therap.2016.04.004","article-title":"Association of the OPRM1 and COMT genes' polymorphisms with the efficacy of morphine in Tunisian cancer patients: impact of the high genetic heterogeneity in Tunisia?","volume":"71","author":"Chatti","year":"2016","journal-title":"Therapie"},{"key":"10.1016\/j.ejphar.2026.179173_bib15","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.29271\/jcpsp.2021.11.1375","article-title":"The influence of OPRM1 A118G polymorphism on the dosage of morphine in patients with advanced liver cancer","volume":"31","author":"Cheng","year":"2021","journal-title":"J. Coll. Physicians Surg.--Pak. JCPSP"},{"key":"10.1016\/j.ejphar.2026.179173_bib16","first-page":"39","article-title":"Establishment of predicting equation for individual sufentanil dosage postoperatively based on gene polymorphisms","volume":"22","author":"Cheng","year":"2022","journal-title":"Pain Pract. Off. J. World Inst. Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib17","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jpain.2019.05.008","article-title":"Systematic review and meta-analysis of genetic risk of developing chronic postsurgical pain","volume":"21","author":"Chidambaran","year":"2020","journal-title":"J. Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib18","author":"Choi"},{"key":"10.1016\/j.ejphar.2026.179173_bib19","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/S0090-9556(25)06378-0","article-title":"Comparative metabolism of hydrocodone in man, rat, Guinea pig, rabbit, and dog","volume":"6","author":"Cone","year":"1978","journal-title":"Drug Metab. Dispos. Biol. Fate Chem."},{"key":"10.1016\/j.ejphar.2026.179173_bib20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-030-81526-4_1","article-title":"History and epidemiology of cancer pain","volume":"182","author":"Copenhaver","year":"2021","journal-title":"Cancer Treat Res."},{"key":"10.1016\/j.ejphar.2026.179173_bib21","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2014-006818","article-title":"Can variability in the effect of opioids on refractory breathlessness be explained by genetic factors?","volume":"5","author":"Currow","year":"2015","journal-title":"BMJ Open"},{"key":"10.1016\/j.ejphar.2026.179173_bib22","series-title":"Medical Genetics Summaries","article-title":"Tramadol therapy and CYP2D6 genotype","author":"Dean","year":"2012"},{"key":"10.1016\/j.ejphar.2026.179173_bib23","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1093\/annonc\/mdn419","article-title":"Prevalence of undertreatment in cancer pain. A review of published literature","volume":"19","author":"Deandrea","year":"2008","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"10.1016\/j.ejphar.2026.179173_bib24","first-page":"115","article-title":"Metabolism and disposition of prescription opioids: a review","volume":"27","author":"DePriest","year":"2015","journal-title":"Forensic Sci. Rev."},{"key":"10.1016\/j.ejphar.2026.179173_bib25","author":"Droney"},{"key":"10.1016\/j.ejphar.2026.179173_bib26","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1515\/prilozi-2016-0019","article-title":"Association of single-nucleotide polymorhism C3435T in the ABCB1 gene with opioid sensitivity in treatment of postoperative pain","volume":"37","author":"Dzambazovska-Trajkovska","year":"2016","journal-title":"PRILOZI"},{"key":"10.1016\/j.ejphar.2026.179173_bib27","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2165\/00003088-200241140-00003","article-title":"Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence","volume":"41","author":"Eap","year":"2002","journal-title":"Clin. Pharmacokinet."},{"key":"10.1016\/j.ejphar.2026.179173_bib28","unstructured":"FDA Approved Drug Products: CODEINE SULFATE Tablets, for Oral Use CII (Jan 2024), n.d."},{"key":"10.1016\/j.ejphar.2026.179173_bib29","unstructured":"FDA Approved Drug Products: Ultram (Tramadol Hydrochloride) Oral Tablets, n.d."},{"key":"10.1016\/j.ejphar.2026.179173_bib30","unstructured":"FDA Label - Methadone, n.d."},{"key":"10.1016\/j.ejphar.2026.179173_bib31","doi-asserted-by":"crossref","first-page":"513","DOI":"10.2217\/pgs-2022-0020","article-title":"ABCB1 and OPRM1 single-nucleotide polymorphisms collectively modulate chronic shoulder pain and dysfunction in South African breast cancer survivors","volume":"23","author":"Firfirey","year":"2022","journal-title":"Pharmacogenomics"},{"key":"10.1016\/j.ejphar.2026.179173_bib32","author":"Frangakis"},{"key":"10.1016\/j.ejphar.2026.179173_bib33","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00280-009-1029-2","article-title":"Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer","volume":"65","author":"Fujita","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.ejphar.2026.179173_bib34","doi-asserted-by":"crossref","DOI":"10.3892\/ol.2023.13941","article-title":"Novel single nucleotide polymorphism biomarkers to predict opioid effects for cancer pain","volume":"26","author":"Fujita","year":"2023","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.ejphar.2026.179173_bib35","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.7314\/APJCP.2013.14.5.2937","article-title":"Gene polymorphisms of OPRM1 A118G and ABCB1 C3435T may influence opioid requirements in Chinese patients with cancer pain","volume":"14","author":"Gong","year":"2013","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"10.1016\/j.ejphar.2026.179173_bib36","first-page":"1906","article-title":"Tramadol pharmacogenetics and tramadol-related adverse events in patients after breast cancer surgery","volume":"27","author":"Goricar","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.ejphar.2026.179173_bib37","doi-asserted-by":"crossref","first-page":"879","DOI":"10.2165\/00003088-200443130-00004","article-title":"Clinical pharmacology of tramadol","volume":"43","author":"Grond","year":"2004","journal-title":"Clin. Pharmacokinet."},{"key":"10.1016\/j.ejphar.2026.179173_bib38","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.pain.2006.07.003","article-title":"Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels","volume":"126","author":"Haeseler","year":"2006","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib39","author":"Hajj"},{"key":"10.1016\/j.ejphar.2026.179173_bib40","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1213\/01.ANE.0000150961.24747.98","article-title":"The effects of tramadol and its metabolite on glycine, gamma-aminobutyric acidA, and N-methyl-D-aspartate receptors expressed in Xenopus oocytes","volume":"100","author":"Hara","year":"2005","journal-title":"Anesth. Analg."},{"key":"10.1016\/j.ejphar.2026.179173_bib41","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1016\/j.pain.2012.03.022","article-title":"Ethnicity interacts with the OPRM1 gene in experimental pain sensitivity","volume":"153","author":"Hastie","year":"2012","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib42","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1038\/s41598-024-54009-9","article-title":"The effects of OPRM1 118A>G on methadone response in pain management in advanced cancer at end of life","volume":"14","author":"Haupt","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejphar.2026.179173_bib43","unstructured":"Health Canada Label - Metadol, n.d."},{"key":"10.1016\/j.ejphar.2026.179173_bib44","unstructured":"Health Canada Monograph - Tramadol, n.d."},{"key":"10.1016\/j.ejphar.2026.179173_bib45","series-title":"Statpearls","article-title":"Mu receptors","author":"Herman","year":"2024"},{"key":"10.1016\/j.ejphar.2026.179173_bib46","unstructured":"Hernandez-Avila, C., Population-specific effects of the Asn40Asp polymorphism at the mu-opioid receptor gene (OPRM1) on HPA-axis activation - PubMed n.d. [WWW Document]. URL https:\/\/pubmed.ncbi.nlm.nih.gov\/18004207\/(accessed 6.15.25)."},{"key":"10.1016\/j.ejphar.2026.179173_bib47","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.jclinane.2011.01.009","article-title":"Persistent pain after mastectomy with reconstruction","volume":"23","author":"Hickey","year":"2011","journal-title":"J. Clin. Anesth."},{"key":"10.1016\/j.ejphar.2026.179173_bib48","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1159\/000487038","article-title":"Association between COMT polymorphism Val158Met and opioid consumption in patients with postoperative pain: a meta-analysis","volume":"26","author":"Hu","year":"2018","journal-title":"Neurosignals"},{"key":"10.1016\/j.ejphar.2026.179173_bib49","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1046\/j.1365-2125.2003.02002.x","article-title":"CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes","volume":"57","author":"Hutchinson","year":"2004","journal-title":"Br. J. Clin. Pharmacol."},{"key":"10.1016\/j.ejphar.2026.179173_bib50","author":"Hwang"},{"key":"10.1016\/j.ejphar.2026.179173_bib51","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1097\/ALN.0000000000000013","article-title":"Effect of catechol-o-methyltransferase-gene (COMT) variants on experimental and acute postoperative pain in 1,000 women undergoing surgery for breast cancer","volume":"119","author":"Kambur","year":"2013","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejphar.2026.179173_bib52","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.jpain.2010.07.011","article-title":"Drug response profiles to experimental pain are opioid and pain modality specific","volume":"12","author":"Kindler","year":"2011","journal-title":"J. Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib53","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.pain.2011.01.040","article-title":"Influence from genetic variability on opioid use for cancer pain: a European genetic association study of 2294 cancer pain patients","volume":"152","author":"Klepstad","year":"2011","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib54","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1111\/j.1399-6576.2004.00517.x","article-title":"The 118 A > G polymorphism in the human mu-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease","volume":"48","author":"Klepstad","year":"2004","journal-title":"Acta Anaesthesiol. Scand."},{"key":"10.1016\/j.ejphar.2026.179173_bib55","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1093\/bja\/aeu186","article-title":"Morphine-6-glucuronide is responsible for the analgesic effect after morphine administration: a quantitative review of morphine, morphine-6-glucuronide, and morphine-3-glucuronide","volume":"113","author":"Klimas","year":"2014","journal-title":"Br. J. Anaesth."},{"key":"10.1016\/j.ejphar.2026.179173_bib56","doi-asserted-by":"crossref","DOI":"10.1016\/j.bjao.2023.100141","article-title":"Opioids and opioid receptors; understanding pharmacological mechanisms as a key to therapeutic advances and mitigation of the misuse crisis","volume":"6","author":"Lambert","year":"2023","journal-title":"BJA Open"},{"issue":"47","key":"10.1016\/j.ejphar.2026.179173_bib57","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1016\/j.ejca.2011.04.014","article-title":"Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids","volume":"1990","author":"Laugsand","year":"2011","journal-title":"Eur. J. Cancer Oxf. Engl."},{"key":"10.1016\/j.ejphar.2026.179173_bib58","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1038\/ctg.2015.19","article-title":"Genetic and non-genetic factors associated with constipation in cancer patients receiving opioids","volume":"6","author":"Laugsand","year":"2015","journal-title":"Clin. Transl. Gastroenterol."},{"issue":"Suppl. 2","key":"10.1016\/j.ejphar.2026.179173_bib59","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1634\/theoncologist.2009-S505","article-title":"Types and epidemiology of cancer-related neuropathic pain: the intersection of cancer pain and neuropathic pain","volume":"15","author":"Lema","year":"2010","journal-title":"Oncologist"},{"key":"10.1016\/j.ejphar.2026.179173_bib60","first-page":"2763","article-title":"The impact of UGT2B7 C802T and CYP3A4*1G polymorphisms on pain relief in cancer patients receiving oxycontin","volume":"26","author":"Li","year":"2018","journal-title":"Support. Care Cancer Off. J. Multinatl. Assoc. Support. Care Cancer"},{"key":"10.1016\/j.ejphar.2026.179173_bib61","doi-asserted-by":"crossref","first-page":"E467","DOI":"10.36076\/ppj.2023.26.E467","article-title":"The effect of genetic variation on the sensitivity to opioid analgesics in patients with postoperative pain: an updated meta-analysis","volume":"26","author":"Li","year":"2023","journal-title":"Pain Physician"},{"key":"10.1016\/j.ejphar.2026.179173_bib62","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1002\/cncr.26430","article-title":"Human mu-opioid receptor gene A118G polymorphism predicts the efficacy of tramadol\/acetaminophen combination tablets (ultracet) in oxaliplatin-induced painful neuropathy","volume":"118","author":"Liu","year":"2012","journal-title":"Cancer"},{"key":"10.1016\/j.ejphar.2026.179173_bib63","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12885-019-5310-4","article-title":"Opioid response in paediatric cancer patients and the Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene: an Italian study on 87 cancer children and a systematic review","volume":"19","author":"Lucenteforte","year":"2019","journal-title":"BMC Cancer"},{"key":"10.1016\/j.ejphar.2026.179173_bib64","doi-asserted-by":"crossref","first-page":"918","DOI":"10.3390\/jpm13060918","article-title":"Pharmacogenetics of lethal opioid overdose: review of Current evidence and preliminary results from a pilot Study","volume":"13","author":"Magarbeh","year":"2023","journal-title":"J. Pers. Med."},{"key":"10.1016\/j.ejphar.2026.179173_bib65","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1213\/ane.0b013e318172fefc","article-title":"The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1","volume":"106","author":"Marincs\u00e1k","year":"2008","journal-title":"Anesth. Analg."},{"key":"10.1016\/j.ejphar.2026.179173_bib66","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.2217\/pgs-2017-0060","article-title":"Advanced cancer pain: the search for genetic factors correlated with interindividual variability in opioid requirement","volume":"18","author":"Matic","year":"2017","journal-title":"Pharmacogenomics"},{"key":"10.1016\/j.ejphar.2026.179173_bib67","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/s41431-021-00920-y","article-title":"Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene\u2013drug interaction between CYP2D6 and opioids (codeine, tramadol and oxycodone)","volume":"30","author":"Matic","year":"2022","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.ejphar.2026.179173_bib68","first-page":"1393","article-title":"Expression changes in arrestin \u03b2 1 and genetic variation in catechol-O-methyltransferase are biomarkers for the response to morphine treatment in cancer patients","volume":"27","author":"Matsuoka","year":"2012","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.ejphar.2026.179173_bib70","doi-asserted-by":"crossref","first-page":"278\u2010e166","DOI":"10.1093\/oncolo\/oyac233","article-title":"Morphine versus oxycodone for cancer pain using a Catechol-O-methyltransferase genotype biomarker: a multicenter, randomized, Open-Label, phase III clinical trial (RELIEF Study)","volume":"28","author":"Matsuoka","year":"2023","journal-title":"Oncologist"},{"key":"10.1016\/j.ejphar.2026.179173_bib71","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1186\/s12885-017-3664-z","article-title":"Selection of opioids for cancer-related pain using a biomarker: a randomized, multi-institutional, open-label trial (RELIEF study)","volume":"17","author":"Matsuoka","year":"2017","journal-title":"BMC Cancer"},{"key":"10.1016\/j.ejphar.2026.179173_bib69","doi-asserted-by":"crossref","first-page":"380","DOI":"10.3892\/br.2017.963","article-title":"Prospective replication study implicates the catechol-O-methyltransferase Val158Met polymorphism as a biomarker for the response to morphine in patients with cancer","volume":"7","author":"Matsuoka","year":"2017","journal-title":"Biomed. Rep"},{"key":"10.1016\/j.ejphar.2026.179173_bib72","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s12529-017-9644-5","article-title":"Expectation of a decrease in pain affects the prognosis of pain in cancer patients: a prospective cohort Study of response to morphine","volume":"24","author":"Matsuoka","year":"2017","journal-title":"Int. J. Behav. Med."},{"key":"10.1016\/j.ejphar.2026.179173_bib73","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med."},{"key":"10.1016\/j.ejphar.2026.179173_bib74","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1002\/phar.2875","article-title":"CYP2D6-guided opioid therapy for adults with cancer pain: a randomized implementation clinical trial","volume":"43","author":"Mosley","year":"2023","journal-title":"Pharmacotherapy"},{"key":"10.1016\/j.ejphar.2026.179173_bib75","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1002\/phar.2875","article-title":"CYP2D6-guided opioid therapy for adults with cancer pain: a randomized implementation clinical trial","volume":"43","author":"Mosley","year":"2023","journal-title":"Pharmacotherapy"},{"key":"10.1016\/j.ejphar.2026.179173_bib76","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1177\/0091270010388033","article-title":"CYP3A5*3 affects plasma disposition of noroxycodone and dose escalation in cancer patients receiving oxycodone","volume":"51","author":"Naito","year":"2011","journal-title":"J. Clin. Pharmacol."},{"key":"10.1016\/j.ejphar.2026.179173_bib77","first-page":"25","article-title":"Tramadol\/Acetaminophen combination tablets in cancer patients with chemotherapy-induced peripheral neuropathy: a single-arm phase II Study","volume":"1","author":"Naruge","year":"2020","journal-title":"Palliat. Med. Rep"},{"key":"10.1016\/j.ejphar.2026.179173_bib78","unstructured":"NCCN (National Comprehensive Cancer Network) Guidelines for patients - stomach cancer, n.d. No Stomach Cancer. URL https:\/\/nostomachforcancer.org\/resource\/nccn-national-comprehensive-cancer-network-guidelines-for-patients-stomach-cancer\/(accessed 9.28.24)."},{"key":"10.1016\/j.ejphar.2026.179173_bib79","first-page":"1319","article-title":"Roles of UGT2B7 C802T gene polymorphism on the efficacy of morphine treatment on cancer pain among the Chinese han population. Niger","volume":"22","author":"Ning","year":"2019","journal-title":"J. Clin. Pract."},{"key":"10.1016\/j.ejphar.2026.179173_bib80","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1097\/AJP.0b013e3182442b1c","article-title":"Natural variation in the \u03bc-opioid gene OPRM1 predicts increased pain on third day after thoracotomy","volume":"28","author":"Ochroch","year":"2012","journal-title":"Clin. J. Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib81","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.2217\/pgs-2016-0082","article-title":"Opioid treatment failure in cancer patients: the role of clinical and genetic factors","volume":"17","author":"Oosten","year":"2016","journal-title":"Pharmacogenomics"},{"issue":"Suppl. 11","key":"10.1016\/j.ejphar.2026.179173_bib82","first-page":"S276","article-title":"Opioid pharmacokinetic drug-drug interactions","volume":"17","author":"Overholser","year":"2011","journal-title":"Am. J. Manag. Care"},{"key":"10.1016\/j.ejphar.2026.179173_bib83","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1097\/ACO.0000000000000660","article-title":"Genetics of perioperative pain management","volume":"31","author":"Packiasabapathy","year":"2018","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"10.1016\/j.ejphar.2026.179173_bib84","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1200\/JCO.22.02198","article-title":"Use of opioids for adults with pain from cancer or Cancer Treatment: ASCO Guideline","volume":"41","author":"Paice","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejphar.2026.179173_bib85","doi-asserted-by":"crossref","first-page":"737","DOI":"10.2217\/pgs-2021-0037","article-title":"Pilot study of multi-gene pharmacogenetic testing for pain management in oncology palliative medicine","volume":"22","author":"Patel","year":"2021","journal-title":"Pharmacogenomics"},{"key":"10.1016\/j.ejphar.2026.179173_bib86","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1186\/1471-2164-12-S3-S9","article-title":"UASIS: universal automatic SNP identification System","volume":"12","author":"Poo","year":"2011","journal-title":"BMC Genom."},{"key":"10.1016\/j.ejphar.2026.179173_bib87","doi-asserted-by":"crossref","first-page":"4","DOI":"10.15360\/1813-9779-2019-6-4-10","article-title":"COMT val158met polymorphism and spinal Analgesia efficacy of laparoscopic surgery for colorectal cancer (a pilot Study)","volume":"15","author":"Potapov","year":"2019","journal-title":"Gen. Reanimatol"},{"key":"10.1016\/j.ejphar.2026.179173_bib88","first-page":"9393","article-title":"Correlation between gene polymorphism and opioid efficacy in patients with gastric or intestinal cancer","volume":"23","author":"Pu","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"10.1016\/j.ejphar.2026.179173_bib89","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.pain.2005.03.032","article-title":"The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients","volume":"116","author":"Rakv\u00e5g","year":"2005","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib90","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1744-8069-4-64","article-title":"Genetic variation in the Catechol-O-Methyltransferase (COMT) gene and morphine requirements in cancer patients with pain","volume":"4","author":"Rakv\u00e5g","year":"2008","journal-title":"Mol. Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib91","doi-asserted-by":"crossref","first-page":"e2042","DOI":"10.1002\/onco.13953","article-title":"Impact of CYP2D6 Pharmacogenomic status on pain control among opioid-treated oncology patients","volume":"26","author":"Reizine","year":"2021","journal-title":"Oncologist"},{"key":"10.1016\/j.ejphar.2026.179173_bib92","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.pain.2006.10.023","article-title":"Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene","volume":"130","author":"Reyes-Gibby","year":"2007","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib93","doi-asserted-by":"crossref","first-page":"573","DOI":"10.2217\/pgs-2021-0021","article-title":"Efficacy and safety of opioid therapy guided by pharmacogenetics: a systematic review","volume":"22","author":"Rodriguez Cairoli","year":"2021","journal-title":"Pharmacogenomics"},{"key":"10.1016\/j.ejphar.2026.179173_bib94","doi-asserted-by":"crossref","DOI":"10.1038\/sj.tpj.6500327","article-title":"Clinical response to morphine in cancer patients and genetic variation in candidate genes","author":"Ross","year":"2005","journal-title":"Pharmacogenomics J."},{"key":"10.1016\/j.ejphar.2026.179173_bib95","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1002\/cncr.23292","article-title":"Genetic variation and response to morphine in cancer patients: catechol-o-methyltransferase and multidrug resistance-1 gene polymorphisms are associated with central side effects","volume":"112","author":"Ross","year":"2008","journal-title":"Cancer"},{"key":"10.1016\/j.ejphar.2026.179173_bib96","article-title":"Opioid system and related ligands: from the past to future perspectives | Journal of Anesthesia","author":"Rullo","year":"2024","journal-title":"Analgesia and Critical Care"},{"key":"10.1016\/j.ejphar.2026.179173_bib97","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.soncn.2019.04.002","article-title":"An overview of cancer pain: epidemiology and pathophysiology","volume":"35","author":"Russo","year":"2019","journal-title":"Semin. Oncol. Nurs."},{"key":"10.1016\/j.ejphar.2026.179173_bib98","author":"Sawinok"},{"key":"10.1016\/j.ejphar.2026.179173_bib99","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s40122-022-00353-5","article-title":"Genetic and clinical factors associated with opioid response in Chinese Han patients with cancer pain: an exploratory cross-sectional Study","volume":"11","author":"Shi","year":"2022","journal-title":"Pain Ther."},{"key":"10.1016\/j.ejphar.2026.179173_bib100","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/sj.bjp.0704703","article-title":"Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing alpha 7 receptors","volume":"136","author":"Shiraishi","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2026.179173_bib101","author":"Simone"},{"key":"10.1016\/j.ejphar.2026.179173_bib102","unstructured":"Sufentanil EMA label, n.d."},{"key":"10.1016\/j.ejphar.2026.179173_bib104","doi-asserted-by":"crossref","first-page":"414","DOI":"10.2133\/dmpk.DMPK-11-RG-134","article-title":"Impact of CYP3A5 and ABCB1 gene polymorphisms on fentanyl pharmacokinetics and clinical responses in cancer patients undergoing conversion to a transdermal system","volume":"27","author":"Takashina","year":"2012","journal-title":"Drug Metabol. Pharmacokinet."},{"key":"10.1016\/j.ejphar.2026.179173_bib105","author":"Tan"},{"key":"10.1016\/j.ejphar.2026.179173_bib106","article-title":"Influence of genetic variants of opioid-related genes on opioid-induced adverse effects in patients with lung cancer: a STROBE-compliant observational study","volume":"100","author":"Tanaka","year":"2021","journal-title":"Medicine (Baltim.)"},{"key":"10.1016\/j.ejphar.2026.179173_bib107","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.cca.2013.12.011","article-title":"Impact of genetic and non-genetic factors on clinical responses to prochlorperazine in oxycodone-treated cancer patients","volume":"429","author":"Tashiro","year":"2014","journal-title":"Clin. Chim. Acta Int. J. Clin. Chem."},{"key":"10.1016\/j.ejphar.2026.179173_bib108","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1093\/annonc\/mdm056","article-title":"Prevalence of pain in patients with cancer: a systematic review of the past 40 years","volume":"18","author":"van den Beuken-van Everdingen","year":"2007","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"10.1016\/j.ejphar.2026.179173_bib109","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2478\/raon-2023-0003","article-title":"Association of OPRM1, MIR23B, and MIR107 genetic variability with acute pain, chronic pain and adverse effects after postoperative tramadol and paracetamol treatment in breast cancer","volume":"57","author":"Vidic","year":"2023","journal-title":"Radiol. Oncol."},{"key":"10.1016\/j.ejphar.2026.179173_bib110","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3949\/ccjm.90a.22019","article-title":"Central sensitization, chronic pain, and other symptoms: better understanding, better management","volume":"90","author":"Volcheck","year":"2023","journal-title":"Cleve. Clin. J. Med."},{"key":"10.1016\/j.ejphar.2026.179173_bib111","author":"Wang"},{"key":"10.1016\/j.ejphar.2026.179173_bib112","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s00228-006-0191-2","article-title":"Effect of the CYP2D6*10 C188T polymorphism on postoperative tramadol analgesia in a Chinese population","volume":"62","author":"Wang","year":"2006","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"10.1016\/j.ejphar.2026.179173_bib113","series-title":"Role of OPRM1, ABCB1 and CYP3A Genetic Polymorphisms on Sufentanil Treatment of Postoperative Cancer Patients in China","author":"Wang","year":"2016"},{"key":"10.1016\/j.ejphar.2026.179173_bib114","unstructured":"Wells, G, et al., n.d. Ottawa Hospital Research Institute [WWW Document]. URL https:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp (accessed 7.25.25)."},{"key":"10.1016\/j.ejphar.2026.179173_bib115","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.autneu.2016.09.017","article-title":"Exploring the multifactorial nature of postoperative nausea and vomiting in women following surgery for breast cancer","volume":"202","author":"Wesmiller","year":"2017","journal-title":"Auton Neurosci. Basic Clin."},{"key":"10.1016\/j.ejphar.2026.179173_bib116","doi-asserted-by":"crossref","DOI":"10.1089\/jpm.2024.0112","article-title":"Influence of COMT (rs4680) and OPRM1 (rs1799971) on Cancer pain, opioid dose, and adverse effects","author":"Wong","year":"2024","journal-title":"J. Palliat. Med."},{"key":"10.1016\/j.ejphar.2026.179173_bib117","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s11864-022-01010-x","article-title":"The role of pharmacogenomics in opioid prescribing","volume":"23","author":"Wong","year":"2022","journal-title":"Curr. Treat. Options Oncol."},{"key":"10.1016\/j.ejphar.2026.179173_bib118","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1089\/gtmb.2014.0318","article-title":"Impact of CYP2D6 polymorphisms on postoperative fentanyl analgesia in gastric cancer patients","volume":"19","author":"Wu","year":"2015","journal-title":"Genet. Test. Mol. Biomark."},{"key":"10.1016\/j.ejphar.2026.179173_bib119","first-page":"3720","article-title":"Effect of opioid-related gene polymorphisms on patients with high-dose opioid-tolerant cancer pain","volume":"99","author":"Xie","year":"2019","journal-title":"Zhonghua Yixue Zazhi"},{"key":"10.1016\/j.ejphar.2026.179173_bib120","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s40360-023-00708-4","article-title":"Study on the association between adverse drug reactions to opioids and gene polymorphisms: a case-case-control study","volume":"24","author":"Yang","year":"2023","journal-title":"BMC Pharmacol. Toxicol."},{"key":"10.1016\/j.ejphar.2026.179173_bib121","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.jpainsymman.2021.03.024","article-title":"Genetic factors associated with pain severity, daily opioid dose requirement, and pain response among advanced cancer patients receiving supportive care","volume":"62","author":"Yennurajalingam","year":"2021","journal-title":"J. Pain Symptom Manag."},{"key":"10.1016\/j.ejphar.2026.179173_bib122","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1097\/AJP.0000000000000636","article-title":"Effects of the OPRM1 A118G polymorphism (rs1799971) on opioid analgesia in cancer pain: a systematic review and meta-analysis","volume":"35","author":"Yu","year":"2019","journal-title":"Clin. J. Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib123","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0304-3959(95)00017-M","article-title":"Validation of world health organization guidelines for cancer pain relief: a 10-year prospective study","volume":"63","author":"Zech","year":"1995","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2026.179173_bib124","first-page":"331","article-title":"The relevance of the OPRM1 118A>G genetic variant for opioid requirement in pain treatment: a meta-analysis","volume":"22","author":"Zhang","year":"2019","journal-title":"Pain Physician"},{"key":"10.1016\/j.ejphar.2026.179173_bib125","doi-asserted-by":"crossref","DOI":"10.1042\/BSR20181211","article-title":"Effects of OPRM1 and ABCB1 gene polymorphisms on the analgesic effect and dose of sufentanil after thoracoscopic-assisted radical resection of lung cancer","volume":"39","author":"Zhao","year":"2019","journal-title":"Biosci. Rep."},{"key":"10.1016\/j.ejphar.2026.179173_bib126","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s12871-023-02120-1","article-title":"Is OPRM1 genotype a valuable predictor of VAS in patients undergoing laparoscopic radical resection of colorectal cancer with fentanyl?","volume":"23","author":"Zhou","year":"2023","journal-title":"BMC Anesthesiol."},{"key":"10.1016\/j.ejphar.2026.179173_bib127","first-page":"5046","article-title":"Correlations of analgesic dosage of morphine with SLC6A4 gene polymorphisms in patients with lung cancer","volume":"24","author":"Zhu","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299926006552?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299926006552?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T20:14:36Z","timestamp":1786652076000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299926006552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":126,"alternative-id":["S0014299926006552"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2026.179173","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Role of genetic polymorphisms on opioid safety and efficacy in cancer pain: A systematic review and meta-analysis","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2026.179173","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"179173"}}