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

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.

Personalized Medicine in Cancer Pain Management

“…TNF was much lower in patients with severe pain, while IL-6 and substance P levels trended downward [ 100 ]. In their observational study, Crescioli et al found that the SNPs of IL6 (rs1800797) and TNF (rs1800629) may serve as possible indicators of baseline pain severity and opioid dosage requirements among pediatric cancer patients [ 40 ]. In a pioneer study, Chang et al investigated the putative participation of cancer-related lncRNAs in endometriosis and detected genetic variants in UCA1, a lncRNA serving as a miRNA sponge, which can be found in endometriosis development and is potentially associated with infertility via regulating lipogenesis [ 101 ].…”

Single nucleotide polymorphisms as predictors of treatment efficacy and adverse effects of morphine in palliative medicine — a literature review

“…Interestingly, patients with at least one copy of the A allele had a significantly lower risk of achieving an NRS pain intensity score of more than 4 points. The SNP rs1800795 for IL-6 may also provide some indication of personal sensitivity to pain stimuli, as the same study revealed that carriers of the G/G genotype in SNP rs1800795 have a higher risk of pre-treatment pain intensity (PI t0 > 4 and ΔVAS > 2) compared to carriers of even one C allele [21].…”

“…A similar relationship was also described for the TNFα rs1800629 SNP -daily and total doses of morphine or other opioids per MED were statistically significantly higher (p = 0.010 and p = 0.031, respectively) in patients with the G/G genotype compared to others. This leads to the conclusion that SNPs for IL-6 and TNF-α may also, in addition to the more extensively studied SNPs described above, be potential indicators of initial pain intensity in oncology patients and, at the same time, a marker of demand for opioids in a particularly important, but less studied, group of paediatric oncology patients [21].…”

“…serine/threonine protein kinase) gene. These SNPs were discovered in genome-wide association studies (GWAS) as a factor for increased post-operative pain levels and the subsequent greater demand for post-operative opioids converted to MEDD [21]. In a study conducted among 110 hospice patients in Canada, the rs1277441 C/T and rs795484 A/G SNPs in the TAOK3 gene were analysed.…”