PURPOSE: 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. EXPERIMENTAL DESIGN: 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. CONCLUSION: 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.
PURPOSE: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 cancerpatients. EXPERIMENTAL DESIGN: We tested 1 million single-nucleotide polymorphisms (SNP) in European cancerpatients, 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 cancerpatients 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. CONCLUSION: Our results indicate that the identified SNP panel can modulate the response of cancerpatients to opioid therapy and may provide a new tool for personalized therapy of cancer pain.
Authors: Mirjam A G Sprangers; Melissa S Y Thong; Meike Bartels; Andrea Barsevick; Juan Ordoñana; Qiuling Shi; Xin Shelley Wang; Pål Klepstad; Eddy A Wierenga; Jasvinder A Singh; Jeff A Sloan Journal: Qual Life Res Date: 2014-03-07 Impact factor: 4.147
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Authors: Asbjørn M Drewes; Rasmus D Jensen; Lecia M Nielsen; Joanne Droney; Lona L Christrup; Lars Arendt-Nielsen; Julia Riley; Albert Dahan Journal: Br J Clin Pharmacol Date: 2013-01 Impact factor: 4.335
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Authors: Cielito C Reyes-Gibby; Jian Wang; Mary Rose T Silvas; Robert Yu; Sai-Ching J Yeung; Sanjay Shete Journal: BMC Genet Date: 2016-02-13 Impact factor: 2.797
Authors: Lin Xu; Raphael A Wilson; Theodore W Laetsch; Dwight Oliver; Sheri L Spunt; Douglas S Hawkins; Stephen X Skapek Journal: Sci Rep Date: 2016-09-19 Impact factor: 4.379