title: Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids.
abstract: BACKGROUND
  This study investigates whether demographical, disease-related and genetic factors contribute to inter-individual differences in nausea and vomiting among patients receiving opioids for cancer pain.
  
  
  METHODS
  Cancer patients receiving opioids were included from 17 centres in 11 European countries. Intensities of nausea and vomiting were reported by 1579 patients on four-point categorical scales. In stratified regression models including demographical and disease-related factors as covariates, 96 single nucleotide polymorphisms (SNPs) in 16 candidate genes related to opioid- or nausea/vomiting signalling pathways (ABCB1, OPRM1, OPRK1, ARRB2, STAT6, COMT, CHRM3, CHRM5, HRH1, DRD2, DRD3, TACR1, HTR3A, HTR3B, HTR3C, CNR1) were analysed for association with nausea and vomiting.
  
  
  RESULTS
  Age, body mass index, Karnofsky Performance Status, gender, use of antiemetics, type of opioid, type of cancer and eight SNPs were associated with the inter-individual differences in nausea and vomiting among cancer patients treated with opioids (p<0.01). The SNPs were rs1176744, rs3782025 and rs1672717 in HTR3B; rs165722, rs4680 and rs4633 in COMT; rs10802789 and rs685550 in CHRM3. Only the SNP rs1672717 in HTR3B passed the Benjamini-Hochberg criterion for a 10% false discovery rate.
  
  
  CONCLUSIONS
  Clinical characteristics and SNPs within the HTR3B, COMT and CHRM3 genes may be associated with the variability in nausea and vomiting among cancer patients receiving opioids. This knowledge may help to identify patients at particular risk for nausea and vomiting during treatment with opioids for cancer pain.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway. eivor.a.laugsand@ntnu.no
authors.forename: Eivor A
authors.initials: EA
authors.lastname: Laugsand
authors.forename: Torill
authors.initials: T
authors.lastname: Fladvad
authors.forename: Frank
authors.initials: F
authors.lastname: Skorpen
authors.forename: Marco
authors.initials: M
authors.lastname: Maltoni
authors.forename: Stein
authors.initials: S
authors.lastname: Kaasa
authors.forename: Peter
authors.initials: P
authors.lastname: Fayers
authors.forename: Pål
authors.initials: P
authors.lastname: Klepstad
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects*; D015992:Body Mass Index; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000209:etiology* / Q000235:genetics*; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction; D014839:Vomiting / Q000209:etiology* / Q000235:genetics*
chemical_list: D000701:Analgesics, Opioid