title: Multiple Loci modulate opioid therapy response for cancer pain.
abstract: OBJECTIVE
  Patients treated with opioid drugs for cancer pain experience different relief responses, raising the possibility that genetic factors play a role in opioid therapy outcome. In this study, we tested the hypothesis that genetic variations may control individual response to opioid drugs in cancer patients.
  
  
  METHODS
  We tested 1 million single-nucleotide polymorphisms (SNP) in European cancer patients, selected in a first series, for extremely poor (pain relief ≤40%; n = 145) or good (pain relief ≥90%; n = 293) responses to opioid therapy using a DNA-pooling approach. Candidate SNPs identified by SNP-array were genotyped in individual samples constituting DNA pools as well as in a second series of 570 patients.
  
  
  RESULTS
  Association analysis in 1,008 cancer patients identified eight SNPs significantly associated with pain relief at a statistical threshold of P < 1.0 × 10⁻³, with rs12948783, upstream of the RHBDF2 gene, showing the best statistical association (P = 8.1 × 10⁻⁹). Functional annotation analysis of SNP-tagged genes suggested the involvement of genes acting on processes of the neurologic system.
  
  
  CONCLUSIONS
  Our results indicate that the identified SNP panel can modulate the response of cancer patients to opioid therapy and may provide a new tool for personalized therapy of cancer pain.
authors.affiliation: Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Galvan
authors.forename: Frank
authors.initials: F
authors.lastname: Skorpen
authors.forename: Pål
authors.initials: P
authors.lastname: Klepstad
authors.forename: Anne Kari
authors.initials: AK
authors.lastname: Knudsen
authors.forename: Torill
authors.initials: T
authors.lastname: Fladvad
authors.forename: Felicia S
authors.initials: FS
authors.lastname: Falvella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pigni
authors.forename: Cinzia
authors.initials: C
authors.lastname: Brunelli
authors.forename: Augusto
authors.initials: A
authors.lastname: Caraceni
authors.forename: Stein
authors.initials: S
authors.lastname: Kaasa
authors.forename: Tommaso A
authors.initials: TA
authors.lastname: Dragani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012697:Serine Endopeptidases; D057057:Serine Proteases / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D057057:Serine Proteases; D012697:Serine Endopeptidases; C545655:RHBDL2 protein, human