Multiple Loci Modulate Opioid Therapy Response for 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 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 x 10(-3), with rs12948783, upstream of the RHBDF2 gene, showing the best statistical association (P = 8.1 x 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. Clin Cancer Res; 17(13); 4581-7. (C) 2011 AACR.