Association of the therapeutic efficacy and toxicity of morphine with polymorphism of drug metabolism-related genes in the treatment of cancer pain

Abstract

Objectives To investigate the relationship of OPRM1 C354A mutations with the clinical efficacy and toxicity of morphine in the treatment of cancer pain. Methods We recruited 100 patients with moderate-severe cancer pain treated at our department from January 2016 to December 2016, and divided them into a CA(wild-type homozygotes)group, a CG(mutated heterozygotes)group, and a GG(homozygous homozygous)group, according to the allele type of OPRM1 C354A.Regular analgesic doses of morphine were given to all groups, and VAS scores and adverse reactions at 2, 4, 8, 16, 24, and 48 hours after analgesia were collected and compared among the groups. Results The OPRM1 C354A mutation groups(CG+ GG)had lower VAS scores at every time point, compared with those of the non-mutation group(CA)(2h: 3.61±0.39 vs.4.04±0.52; 4h: 3.88±0.41 vs.4.20±0.15; 8h: 3.95±0.32 vs.4.37±0.24; 16h: 3.81±0.38 vs.4.33±0.15; 24h: 3.84±0.25 vs.4.42±0.18; and 48h: 3.86±0.20 vs.4.41±0.14)(t=4.648, 5.261, 7.461, 8.454, 13.389, and 16.030, respectively, each P=0.000). The incidences of constipation(23.08% vs.6.25%)and vertigo(25% vs.8.33%)in the OPRM1 C354A mutation groups(CG+ GG)were significantly higher than those in the non-mutation group(CA)(χ2=5.543 and 4.914, P=0.019 and 0.027, respectively). Conclusions Polymorphism of the OPRM1 C354A gene is associated with the clinical efficacy and toxicity of morphine in the treatment of cancer pain. Key words: Morphine; Cancer pain; OPRM1; gene polymorphisms; toxicities