Department of Clinical and Experimental Medicine University of Pisa, Pisa, Italy.
Department of Neuroscience, Psychology, Drug Research and Children's Health, University of Florence, Florence, Italy.
BMC Cancer. 2019 Jan 31;19(1):113. doi: 10.1186/s12885-019-5310-4.
Genetic polymorphisms in genes involved in pain modulation have been reported to be associated to opioid efficacy and safety in different clinical settings.
The association between COMT Val158Met polymorphism (rs4680) and the inter-individual differences in the response to opioid analgesic therapy was investigated in a cohort of 87 Italian paediatric patients receiving opioids for cancer pain (STOP Pain study). Furthermore, a systematic review of the association between opioid response in cancer patients and the COMT polymorphism was performed in accordance with the Cochrane Handbook and the Prisma Statement.
In the 87 paediatric patients, pain intensity (total time needed to reach the lowest possible level) was significantly higher for G/G than A/G and A/A carriers (p-value = 0.042). In the 60 patients treated only with morphine, the mean of total dose to reach the same pain intensity was significantly higher for G/G than A/G and A/A carriers (p-value = 0.010). Systematic review identified five studies on adults, reporting that opioid dose (mg after 24 h of treatment from the first pain measurement) was higher for G/G compared to A/G and A/A carriers.
Present research suggests that the A allele in COMT polymorphism could be a marker of opioid sensitivity in paediatric cancer patients (STOP Pain), as well as in adults (Systematic Review), indicating that the polymorphism impact could be not age-dependent in the cancer pain context.
Registration number: CRD42017057831 .
已报道在不同临床环境中，参与疼痛调节的基因中的遗传多态性与阿片类药物的疗效和安全性有关。
在接受阿片类药物治疗癌症疼痛的 87 名意大利儿科患者队列（STOP Pain 研究）中，研究了 COMT Val158Met 多态性（rs4680）与阿片类药物镇痛治疗个体间反应差异的相关性。此外，根据 Cochrane 手册和 Prisma 声明，对癌症患者阿片类药物反应与 COMT 多态性的相关性进行了系统评价。
在 87 名儿科患者中，G/G 比 A/G 和 A/A 携带者的疼痛强度（达到最低可能水平所需的总时间）显著更高（p 值=0.042）。在仅接受吗啡治疗的 60 名患者中，达到相同疼痛强度所需的总剂量，G/G 比 A/G 和 A/A 携带者明显更高（p 值=0.010）。系统评价确定了五项关于成年人的研究，报告称阿片类药物剂量（从首次疼痛测量后 24 小时的治疗开始时的 mg）在 G/G 比 A/G 和 A/A 携带者中更高。
目前的研究表明，COMT 多态性中的 A 等位基因可能是儿科癌症患者（STOP Pain）以及成年人（系统评价）中阿片类药物敏感性的标志物，表明在癌症疼痛背景下，多态性的影响可能与年龄无关。
注册号：CRD42017057831。
