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
Ersilia Lucenteforte,
Alfredo Vannacci,
Giada Crescioli,
Niccolò Lombardi,
Laura Vagnoli,
Laura Giunti,
Valentina Cetica,
Maria Luisa Coniglio,
Alessandra Pugi,
Roberto Bonaiuti,
Maurizio Aricò,
Sabrina Giglio,
Andrea Messeri,
Roberto Barale,
Lisa Giovannelli,
Alessandro Mugelli,
Valentina Maggini
Affiliations
Ersilia Lucenteforte
Department of Clinical and Experimental Medicine University of Pisa
Alfredo Vannacci
Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence
Giada Crescioli
Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence
Niccolò Lombardi
Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence
Laura Vagnoli
Pain and Palliative Care Unit, Meyer Children’s University Hospital
Laura Giunti
Medical Genetics Unit, Meyer Children’s University Hospital
Valentina Cetica
Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience Department, Meyer Children’s University Hospital, University of Florence
Maria Luisa Coniglio
Department of Paediatric Oncohematology, Meyer Children’s University Hospital
Alessandra Pugi
Clinical Trial Office, Meyer Children’s University Hospital
Roberto Bonaiuti
Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence
Maurizio Aricò
Direzione Generale, Azienda Sanitaria Provinciale
Sabrina Giglio
Medical Genetics Unit, Meyer Children’s University Hospital
Andrea Messeri
Pain and Palliative Care Unit, Meyer Children’s University Hospital
Roberto Barale
Department of Biology, University of Pisa
Lisa Giovannelli
Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence
Alessandro Mugelli
Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence
Valentina Maggini
Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence
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.
