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This study aimed at identifying associations between <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s of candidate genes, high opioid dose, and cognitive dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cross\u2010sectional multicenter study (European Pharmacogenetic Opioid Study, 2005\u20132008); 1586 patients; 113 <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s from 41 genes. Inclusion criteria: cancer, age \u226518\u00a0year, opioid treatment, and available genetic data. Cognitive assessment by Mini\u2010Mental State Examination (<jats:styled-content style=\"fixed-case\">MMSE<\/jats:styled-content>). Analyses: <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s were rejected if violation of Hardy\u2013Weinberg equilibrium (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0005), or minor allele frequency &lt;5%; patients were randomly divided into discovery sample (2\/3 for screening) and validation sample (1\/3 for confirmatory test); false discovery rate of 10% for determining associations (Benjamini\u2013Hochberg method). Co\u2010dominant, dominant, and recessive models were analyzed by Kruskal\u2013Wallis and Mann\u2013Whitney tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the co\u2010dominant model significant associations (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) between <jats:styled-content style=\"fixed-case\">MMSE<\/jats:styled-content> scores and <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s in the <jats:italic><jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>3E<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">TACR<\/jats:styled-content>1<\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>6<\/jats:italic> were observed in the discovery sample, but the replication in the validation sample did not confirm it. Associations between <jats:styled-content style=\"fixed-case\">MMSE<\/jats:styled-content> scores among patients receiving \u2265400\u00a0mg morphine equivalent dose\/day and <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s in <jats:italic><jats:styled-content style=\"fixed-case\">TNFRSF<\/jats:styled-content>1B<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>5<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>2A<\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">ADRA<\/jats:styled-content>2A<\/jats:italic> were observed, but they could not be confirmed in the validation sample. After correction for multiple testing, no <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s were significant in the discovery sample. Dominant and recessive models also did not confirm significant associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The findings did not support influence of those <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s analyzed to explain cognitive dysfunction in opioid\u2010treated patients with cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.471","type":"journal-article","created":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T16:19:05Z","timestamp":1462378745000},"source":"Crossref","is-referenced-by-count":14,"title":["Genetic variation and cognitive dysfunction in opioid\u2010treated patients with cancer"],"prefix":"10.1002","volume":"6","author":[{"given":"Geana Paula","family":"Kurita","sequence":"first","affiliation":[{"name":"Multidisciplinary Pain Centre Department of Neuroanaesthesiology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark"},{"name":"Department of Oncology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Ekholm","sequence":"additional","affiliation":[{"name":"National Institute of Public Health University of Southern Denmark Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stein","family":"Kaasa","sequence":"additional","affiliation":[{"name":"Department of Oncology Oslo University Hospital\/University of Oslo Norway"},{"name":"European Palliative Care Research Centre Faculty of Medicine Norwegian University of Science and Technology Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e5l","family":"Klepstad","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine St Olavs Hospital Trondheim University Hospital Trondheim Norway"},{"name":"Department of Circulation and Medical Imaging Norwegian University of Science and Technology Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Skorpen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Children's and Women's Health Norwegian University of Science and Technology Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Sj\u00f8gren","sequence":"additional","affiliation":[{"name":"Section\u00a0of Palliative Medicine Department of Oncology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark"},{"name":"Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-7-9"},{"key":"e_1_2_7_3_1","first-page":"854527","article-title":"Intereleukin\u201010 promoter polymorphism in mild cognitive impairment and in its clinical evolution","author":"Arosio B.","year":"2010","journal-title":"Int. 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