STOP Pain Project—Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways
Giada Crescioli,
Niccolò Lombardi,
Laura Vagnoli,
Alessandra Bettiol,
Laura Giunti,
Valentina Cetica,
Maria Luisa Coniglio,
Aldesia Provenzano,
Sabrina Giglio,
Roberto Bonaiuti,
Alessandro Mugelli,
Maurizio Aricò,
Andrea Messeri,
Alfredo Vannacci,
Valentina Maggini
Affiliations
Giada Crescioli
Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence, 50139 Florence, Italy
Niccolò Lombardi
Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence, 50139 Florence, Italy
Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy
Laura Giunti
Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, 50139 Florence, Italy
Valentina Cetica
Laboratory of Neurogenetics, Pediatric Neurology Unit, Meyer Children’s Hospital, 50139 Florence, Italy
Maria Luisa Coniglio
Centre of Excellence, Division of Pediatric Oncology/Hematology, Meyer Children’s Hospital, 50139 Florence, Italy
Aldesia Provenzano
Medical Genetics Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy
Sabrina Giglio
Medical Genetics Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50139 Florence, Italy
Roberto Bonaiuti
Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence, 50139 Florence, Italy
Alessandro Mugelli
Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence, 50139 Florence, Italy
Maurizio Aricò
Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, 50139 Florence, Italy
Andrea Messeri
Pain and Palliative Care Unit, Meyer Children’s Hospital, 50139 Florence, Italy
Alfredo Vannacci
Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence, 50139 Florence, Italy
Valentina Maggini
Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Children’s Health, University of Florence, 50139 Florence, Italy
Moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Pharmacogenetics play a central role in developing personalized pain therapies, as well as avoiding treatment failure and/or intolerable adverse drug reactions. This observational study aimed to investigate the association between IL-6, IL-8, and TNFα genetic single nucleotide polymorphisms (SNPs) and response to opioid therapy in a cohort of pediatric cancer patients. Pain intensity before treatment (PIt0) significantly differed according to IL-6 rs1800797 SNP, with a higher PI for A/G and G/G individuals (p = 0.017), who required a higher dose of opioids (p = 0.047). Moreover, compared to G/G subjects, heterozygous or homozygous individuals for the A allele of IL-6 rs1800797 SNP had a lower risk of having a PIt0 > 4. Dose24h and Dosetot were both higher in G/G individuals for TNFα rs1800629 (p = 0.010 and p = 0.031, respectively), while risk of having a PIt0 > 4 and a ∆VAS > 2 was higher for G/G subjects for IL-6 rs1800795 SNP compared to carriers of the C allele. No statistically significant association between genotypes and safety outcomes was found. Thus, IL-6 and TNFα SNPs could be potential markers of baseline pain intensity and opioid dose requirements in pediatric cancer patients.
