Genetic Factors Associated With Pain Severity, Daily Opioid Dose Requirement, and Pain Response Among Advanced Cancer Patients Receiving Supportive Care
Genetic Factors Associated With Pain Severity, Daily Opioid Dose Requirement, and Pain Response Among Advanced Cancer Patients Receiving Supportive Care
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DOI：
10.1016/j.jpainsymman.2021.03.024
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发表时间：
2021-09-28
影响因子：
4.7
通讯作者：
Bruera，Eduardo
中科院分区：
文献类型：
--
作者：
Yennurajalingam，Sriram;Astolfi，Annalisa;Bruera，Eduardo
背景目前对与疼痛严重程度相关的遗传因素以及阿片类药物对晚期癌症患者（AC）疼痛的改善的理解不足以提供个性化的疼痛治疗（PPT）。因此，本研究的目的是确定与疼痛的严重程度，每日阿片类药物剂量和疼痛反应的AC患者接受支持care.MethodsIn这项前瞻性研究，AC患者有资格，如果他们有癌症疼痛≥4/10埃德蒙顿症状评估量表（ESAS）-疼痛项目，并需要阿片类药物的旋转疼痛控制专家在门诊支持护理中心。使用逻辑回归模型和SKATO（基因块）analysis.ResultsAbout 174/178（98%）患者样本进行了分析，遗传因素与疼痛表型的关联进行了评估。在调整人口统计学和临床变量后，疼痛严重程度与OPRM 1 rs 9322446，P= 0.02; rs 2270459，P= 0.038; rs62052210，P= 0.038的内含子变异等位基因呈负相关。阿片类药物日剂量与NFKBIA rs 2233419，P= 0.008; rs 2233417，P= 0.007; rs3138054，P= 0.008; rs 1050851，P= 0.015; ORPM 1 rs 9479759，P= 0.046; rs 2003185，P= 0.047; rs636433，P= 0.044; COMT（rs9306234，P= 0.014; rs165728，P= 0.014; rs2020917，P= 0.036; rs165728，P= 0.034）; ARRB 2（rs 1045280，P= 0.045）;阿片类药物的疼痛反应与OPRM 1 rs 1319339，P= 0.024; rs34427887，P= 0.048;和COMT rs 4646316，P= 0.03呈负相关; rs35478083，P= 0.028。SKATO分析显示疼痛严重程度与CXCL 8之间存在关联（P= 0.0056）和STAT 6（P= 0.0297）基因，与IL-6的疼痛反应结论OPRM 1、COMT、NFKBIA、CXCL 8、IL-6、STAT 6和ARRB 2基因的SNP与疼痛程度、阿片类药物日剂量、和疼痛反应。需要更多的研究来验证我们对PPT的发现。
BackgroundCurrent understanding of genetic factors associated with pain severity, and improvement of pain with opioids in advanced cancer patients (AC) is inadequate for delivery of personalized pain therapy (PPT). Therefore, the aim of this study was to determine the genetic factors associated with pain severity, daily opioid dose, and pain response in AC patients receiving supportive care.MethodsIn this prospective study, AC patients were eligible if they had cancer pain ≥4/10 on Edmonton Symptom Assessment Scale (ESAS) - Pain Item and needed opioid rotation for pain control by specialist at the outpatient supportive care center. Association of genetic factors with pain phenotype was assessed using logistic regression models and SKATO (Gene-block) analysis.ResultsAbout 174/178 (98%) patient samples were analyzed. After adjustment for demographic and clinical variables, pain severity was negatively associated with intron variant alleles in OPRM1 rs9322446,P= 0.02; rs2270459,P= 0.038; rs62052210,P= 0.038. Opioid daily dose was positively associated NFKBIA rs2233419,P= 0.008; rs2233417,P= 0.007; rs3138054,P= 0.008; rs1050851,P= 0.015; ORPM1 rs9479759,P= 0.046; rs2003185,P= 0.047; rs636433,P= 0.044; COMT (rs9306234,P= 0.014; rs165728,P= 0.014; rs2020917,P= 0.036; rs165728,P= 0.034); ARRB2 (rs1045280,P= 0.045); and pain response to opioids was negatively associated OPRM1 rs1319339,P= 0.024; rs34427887,P= 0.048; and COMT rs4646316,P= 0.03; rs35478083,P= 0.028, respectively. SKATO analysis showed association between pain severity and CXCL8 (P= 0.0056), and STAT6 (P= 0.0297) genes respectively, and pain response with IL-6 (P= 0.00499).ConclusionsThis study identified that SNPs of OPRM1, COMT, NFKBIA, CXCL8, IL-6, STAT6, and ARRB2 genes were associated with pain severity, opioid daily dose, and pain response in AC receiving supportive care. Additional studies are needed to validate our findings for PPT.