Department of Palliative care, Rehabilitation Medicine, and Integrative Medicine UT MD Anderson Cancer Center (S.Y., C.R.-G., Z.L., J.L.W., S.-C.Y., A.E.A., E.B.), Houston, Texas.
"Giorgio Prodi" Center for Cancer Research, Alma Mater Studiorum, University of Bologna (A.A., V.I., A.S., G.B.), Bologna, Italy; Department of Morphology, Surgery and Experimental Medicine, University of Ferrara (A.A.), Ferrara, Italy.
J Pain Symptom Manage. 2021 Oct;62(4):785-795. doi: 10.1016/j.jpainsymman.2021.03.024. Epub 2021 Apr 10.
Current 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.
In 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.
About 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).
This 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.
目前对于与晚期癌症患者（AC）疼痛严重程度以及阿片类药物改善疼痛相关的遗传因素的了解，不足以提供个性化疼痛治疗（PPT）。因此，本研究旨在确定与 AC 患者接受支持性护理时疼痛严重程度、每日阿片类药物剂量和疼痛反应相关的遗传因素。
在这项前瞻性研究中，符合条件的 AC 患者为癌症疼痛≥4/10 分（ESAS 疼痛项目）且需要专家在门诊支持治疗中心进行阿片类药物轮换以控制疼痛的患者。使用逻辑回归模型和 SKATO（基因块）分析评估遗传因素与疼痛表型的相关性。
约 174/178（98%）患者样本进行了分析。在调整人口统计学和临床变量后，疼痛严重程度与 OPRM1 rs9322446、P=0.02 的内含子变异等位基因呈负相关；rs2270459、P=0.038；rs62052210、P=0.038 呈负相关。每日阿片类药物剂量与 NFKBIA rs2233419、P=0.008；rs2233417、P=0.007；rs3138054、P=0.008；rs1050851、P=0.015；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)；阿片类药物疼痛反应与 OPRM1 rs1319339、P=0.024；rs34427887、P=0.048；COMT rs4646316、P=0.03；rs35478083、P=0.028 分别呈负相关。SKATO 分析显示，疼痛严重程度与 CXCL8（P=0.0056）和 STAT6（P=0.0297）基因相关，疼痛反应与 IL-6（P=0.00499）相关。
本研究发现 OPRM1、COMT、NFKBIA、CXCL8、IL-6、STAT6 和 ARRB2 基因的 SNP 与接受支持性护理的 AC 患者的疼痛严重程度、每日阿片类药物剂量和疼痛反应相关。需要进一步的研究来验证我们的发现是否适用于 PPT。
