title: Genetic variation and cognitive dysfunction in opioid-treated patients with cancer.
abstract: The effects of single-nucleotide polymorphisms (SNPs) on the cognitive function of opioid-treated patients with cancer until now have not been explored, but they could potentially be related to poor functioning. This study aimed at identifying associations between SNPs of candidate genes, high opioid dose, and cognitive dysfunction.
  
  
  
  Cross-sectional multicenter study (European Pharmacogenetic Opioid Study, 2005-2008); 1586 patients; 113 SNPs from 41 genes.
  
  
  
  cancer, age ≥18 year, opioid treatment, and available genetic data. Cognitive assessment by Mini-Mental State Examination (MMSE).
  
  
  
  SNPs were rejected if violation of Hardy-Weinberg equilibrium (P < 0.0005), or minor allele frequency <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-Hochberg method). Co-dominant, dominant, and recessive models were analyzed by Kruskal-Wallis and Mann-Whitney tests.
  
  
  
  In the co-dominant model significant associations (P < 0.05) between MMSE scores and SNPs in the HTR3E,TACR1, and IL6 were observed in the discovery sample, but the replication in the validation sample did not confirm it. Associations between MMSE scores among patients receiving ≥400 mg morphine equivalent dose/day and SNPs in TNFRSF1B,TLR5,HTR2A, and ADRA2A were observed, but they could not be confirmed in the validation sample. After correction for multiple testing, no SNPs were significant in the discovery sample. Dominant and recessive models also did not confirm significant associations.
  
  
  
  The findings did not support influence of those SNPs analyzed to explain cognitive dysfunction in opioid-treated patients with cancer.
authors.affiliation: Multidisciplinary Pain Centre Department of Neuroanaesthesiology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark; Department of Oncology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.
authors.forename: Geana Paula
authors.initials: GP
authors.lastname: Kurita
authors.affiliation: National Institute of Public Health University of Southern Denmark Copenhagen Denmark.
authors.forename: Ola
authors.initials: O
authors.lastname: Ekholm
authors.affiliation: Department of Oncology Oslo University Hospital/University of Oslo Norway; European Palliative Care Research Centre Faculty of Medicine Norwegian University of Science and Technology Trondheim Norway.
authors.forename: Stein
authors.initials: S
authors.lastname: Kaasa
authors.affiliation: Department of Intensive Care Medicine St Olavs Hospital Trondheim University Hospital Trondheim Norway; Department of Circulation and Medical Imaging Norwegian University of Science and Technology Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Klepstad
authors.affiliation: Department of Laboratory Medicine Children's and Women's Health Norwegian University of Science and Technology Trondheim Norway.
authors.forename: Frank
authors.initials: F
authors.lastname: Skorpen
authors.affiliation: Section of Palliative Medicine Department of Oncology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark; Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Sjøgren
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects*; D000072716:Cancer Pain / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011897:Random Allocation; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid
keywords: Cognition; genes; neoplasms; opioids; polymorphism; single nucleotide