Opioid response in paediatric cancer patients and the Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene: an Italian study on 87 cancer children and a systematic review

BMC Cancer. 2019 Jan 31;19(1):113. doi: 10.1186/s12885-019-5310-4.

Abstract

Background: Genetic polymorphisms in genes involved in pain modulation have been reported to be associated to opioid efficacy and safety in different clinical settings.

Methods: The association between COMT Val158Met polymorphism (rs4680) and the inter-individual differences in the response to opioid analgesic therapy was investigated in a cohort of 87 Italian paediatric patients receiving opioids for cancer pain (STOP Pain study). Furthermore, a systematic review of the association between opioid response in cancer patients and the COMT polymorphism was performed in accordance with the Cochrane Handbook and the Prisma Statement.

Results: In the 87 paediatric patients, pain intensity (total time needed to reach the lowest possible level) was significantly higher for G/G than A/G and A/A carriers (p-value = 0.042). In the 60 patients treated only with morphine, the mean of total dose to reach the same pain intensity was significantly higher for G/G than A/G and A/A carriers (p-value = 0.010). Systematic review identified five studies on adults, reporting that opioid dose (mg after 24 h of treatment from the first pain measurement) was higher for G/G compared to A/G and A/A carriers.

Conclusions: Present research suggests that the A allele in COMT polymorphism could be a marker of opioid sensitivity in paediatric cancer patients (STOP Pain), as well as in adults (Systematic Review), indicating that the polymorphism impact could be not age-dependent in the cancer pain context.

Trial registration: Registration number: CRD42017057831 .

Keywords: Cancer pain; Children; Genetic polymorphisms; Opioid; Systematic review.

Publication types

  • Systematic Review

MeSH terms

  • Adolescent
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / blood
  • Cancer Pain / drug therapy*
  • Cancer Pain / genetics*
  • Catechol O-Methyltransferase / genetics*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Italy
  • Male
  • Morphine / administration & dosage*
  • Morphine / blood
  • Pain Measurement / statistics & numerical data
  • Polymorphism, Single Nucleotide

Substances

  • Analgesics, Opioid
  • Morphine
  • COMT protein, human
  • Catechol O-Methyltransferase