Dual single‑nucleotide polymorphism biomarker combination for opioid selection to treat cancer pain.

We have been exploring biomarkers that could help physicians select the appropriate opioid for individualized treatment of cancer pain. Recently, we identified a single nucleotide polymorphism (SNP) of (rs17809012) as one such biomarker that was significantly associated with the analgesic effect of morphine. The current study measured the plasma concentrations of chemokines/cytokines in pre-treatment plasma samples of a total of 138 patients who were randomized to receive morphine (n=70) or oxycodone (n=68). Based on the results, one cytokine, IL-16, was identified whose plasma concentrations showed a clear bias between patients with cancer pain who responded well and responded poorly to oxycodone. A genotypic analysis also identified a SNP of the gene (rs4778889) as being significantly associated with the analgesic effect of oxycodone. Whether both of the SNPs identified as being significant ( rs17809012 and rs4778889) could be used in combination to accurately predict which opioid might be the most suitable to provide pain relief in patients with cancer was assessed. Morphine tended to provide superior analgesic effect over oxycodone in patients with the rs4778889 TT genotype and the rs17809012 AG/GG genotype (n=45), while a trend towards a greater analgesic effect of oxycodone was observed in patients with other genotype combinations of these SNPs (n=93) (P=0.0012 for the interaction), suggesting that the rs4778889 and rs17809012 SNPs could serve as a potential dual-biomarker combination for personalized analgesic therapy in patients with cancer pain.