Role of Genetic Polymorphisms on Opioid Safety and Efficacy in Cancer Pain: A Systematic Review and Meta-Analysis.

Candidate variants of the mu receptor (OPRM1 rs1799971), the ABCB1 transporter (rs1045642) and COMT (rs4680): modest, context-dependent effects.

Systematic review and seven meta-analyses across 24 independent populations (n = 4,190) of patients with cancer receiving opioids, focused on the three most studied variants: OPRM1 rs1799971, ABCB1 rs1045642 and COMT rs4680. No significant association with opioid dose requirements was found for any of the three variants. The only exception was a subgroup restricted to acute pain, where OPRM1 rs1799971 GG carriers required higher doses than AA carriers (standardised mean difference +0.61; 95% CI 0.04-1.18), an effect absent in chronic pain. Meta-analyses of pain scores and adverse effects (nausea, vomiting, constipation) for OPRM1 were also non-significant, and the qualitative review of 73 studies covering CYP2D6, UGT2B7, CYP3A4, CYP3A5, OPRK1, OPRD1, HTR3B and STAT6 proved heterogeneous and often underpowered.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A useful negative result: there is no case for genotyping OPRM1, COMT or ABCB1 to adjust opioid therapy in cancer pain, and this review states it with a level of evidence rarely reached for these three variants. The single positive signal, in acute postoperative pain, has a confidence interval bordering on null and does not justify testing. That said, the real pharmacogenetic lever in analgesia, CYP2D6 for codeine and tramadol, is not settled here and is covered only qualitatively.

Analysis by Dr Thibaut Benquey