• Antonella Galvan, Frank Skorpen, Pål Klepstad, Anne Kari Knudsen, Torill Fladvad, Felicia S Falvella, Alessandra Pigni, Cinzia Brunelli, Augusto Caraceni, Stein Kaasa, and Tommaso A Dragani.
• Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
• Clin Cancer Res. 2011 Jul 1; 17 (13): 4581-7.

PurposePatients 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 DesignWe 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.ResultsAssociation 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.ConclusionOur 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.

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