Genetic Profile and Cancer‐Related Pain: A Tale from Two Outlier Cases with Bone Metastatic Disease

Dear Editor, Morphine is the mainstay of pharmacological treatment for moderate-to-severe cancer-related pain. However, different analgesic response is an important problem in palliative care [1]. Genetic variations seems to represent an important cause of this interindividual variability in polymorphisms of opioid receptors, transporters, and metabolizing enzymes, as well as in modulators/suppressors involved in perception and processing of pain information [1]. Therefore, genetic study of outlier cases might be an excellent opportunity to analyze the influence of some single-nucleotide polymorphisms (SNP) in nociception and morphine requirements. Here, we present the study of a genetic profile of two cases: one patient considered a low responder (Patient 1) and one considered sensitive to morphine (Patient 2), requiring about 40-fold less morphine. The difference in morphine requirements prompted us to study SNP that include different phases of analgesic response: μ-opioid receptor (OPRM1; rs1799971), catechol-O-methyltransferase (COMT; rs4680), multidrug resistance protein 1 (ABCB1; rs1128503, rs1045642), organic anion-transporting polypeptides 1A2 (OATP1A2; rs11568563), and UDP-glucuronosyltransferase-2B7 (UGT2B7; hCV32449742: rs7439366, rs7438284). Plasma concentrations of morphine and major metabolites (morphine-3-glucuronide (M3G) and morphine-6-glucuronide [M6G]) were also determined [2] and metabolic ratios were calculated. The first patient, a 23-year-old female presenting an osteosarcoma, bone metastasis, and complains of mixed pain (nociceptive and neuropathic pain), was receiving 800 mg/day of morphine. Coadministered drugs were gabapentin (1700 mg/day) and prednisolone (20 mg/day). Despite medication, the pain relief was not adequate, …