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

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 TNF alpha 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. Dose(24h) and Dose(tot) were both higher in G/G individuals for TNF alpha rs1800629 (p = 0.010 and p = 0.031, respectively), while risk of having a PIt0 > 4 and a increment (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 TNF alpha SNPs could be potential markers of baseline pain intensity and opioid dose requirements in pediatric cancer patients.