STOP Pain Project-Opioid Response in Pediatric Cancer Patients and Gene Polymorphisms of Cytokine Pathways.

Giada Crescioli,Laura Vagnoli,Aldesia Provenzano,Alessandra Bettiol,Roberto Bonaiuti,Maria Luisa Coniglio,Valentina Maggini,Laura Giunti,Alessandro Mugelli,Valentina Cetica,Maurizio Aricò,Andrea Messeri,Alfredo Vannacci,Sabrina Giglio,Niccolò Lombardi

doi:10.3390/pharmaceutics14030619

Abstract

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.

Highlights

In children under the age of 14, cancer incidence reaches 150 per million person-years in the populations of North America and Europe
Half of the patients reported the oral cavity as the pain location, with a mean value of PIt0 of 4.32 points
Risk of having a PIt0 > 4 and a ∆VAS > 2 was higher for G/G subjects for IL-6 rs1800795 single nucleotide polymorphisms (SNPs) compared to carriers of the C allele, both heterozygous or homozygous: OR 5.00 and OR 4.75, respectively

Summary

Introduction

In children under the age of 14, cancer incidence reaches 150 per million person-years in the populations of North America and Europe. The distribution of cancer type varies in age groups, with leukemia, central nervous system (CNS) tumors, and lymphomas as the most common types of cancers [1]. More recent evidence report ∼178 cases per million in Europe and North America, and up to ∼218 cases per million in West and Middle Africa [2]. According to 2012 World Health Organization guidelines [3], as for adults, moderate to severe cancer pain treatment in children is based on the use of weak and strong opioids. Single nucleotide polymorphisms (SNPs) of genes involved in the pharmacokinetics and pharmacodynamics of drugs play a central role in developing personalized therapies for pain, avoiding failure of treatment or intolerable adverse drug reactions (ADRs) [6]

Methods

Results

Conclusion