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

• Published in: Pharmaceutics Vol. 14; no. 3; p. 619
• Main Authors: Crescioli, Giada, Lombardi, Niccolò, Vagnoli, Laura, Bettiol, Alessandra, Giunti, Laura, Cetica, Valentina, Coniglio, Maria Luisa, Provenzano, Aldesia, Giglio, Sabrina, Bonaiuti, Roberto, Mugelli, Alessandro, Aricò, Maurizio, Messeri, Andrea, Vannacci, Alfredo, Maggini, Valentina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.03.2022; MDPI
• Subjects: Age; Body mass index; cancer; Cancer therapies; Cytokines; Disease; Drug dosages; Fentanyl; Genes; genetic polymorphisms; Haplotypes; Leukemia; Lung cancer; Metastasis; Morphine; Narcotics; Nervous system; opioid; Pain; Pediatrics; pharmacogenetics; Tumor necrosis factor-TNF; Tumors; North America; Europe; pain; children; opioid; cancer; cytokines; genetic polymorphisms; pharmacogenetics
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14030619

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.