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
Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Children's Health, University of Florence, 50139 Florence, Italy.
Tuscan Regional Centre of Pharmacovigilance, 50122 Florence, Italy.
Pharmaceutics. 2022 Mar 11;14(3):619. 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.
儿童中重度癌痛治疗基于使用弱效和强效阿片类药物。药物遗传学在制定个性化疼痛治疗方案以及避免治疗失败和/或难以耐受的药物不良反应方面发挥着核心作用。这项观察性研究旨在调查白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和肿瘤坏死因子α（TNFα）基因单核苷酸多态性（SNP）与一组儿科癌症患者阿片类药物治疗反应之间的关联。根据IL-6 rs1800797 SNP，治疗前疼痛强度（PIt0）存在显著差异，A/G和G/G个体的疼痛强度较高（p = 0.017），他们需要更高剂量的阿片类药物（p = 0.047）。此外，与G/G受试者相比，IL-6 rs1800797 SNP的A等位基因杂合或纯合个体的PIt0>4的风险较低。对于TNFα rs1800629，G/G个体的24小时剂量（Dose24h）和总剂量（Dosetot）均较高（分别为p = 0.010和p = 0.031），而与C等位基因携带者相比，IL-6 rs1800795 SNP的G/G受试者的PIt0>4和视觉模拟评分变化（∆VAS）>2的风险更高。未发现基因型与安全性结果之间存在统计学显著关联。因此，IL-6和TNFα SNPs可能是儿科癌症患者基线疼痛强度和阿片类药物剂量需求的潜在标志物。
