吗啡在癌痛治疗中疗效和毒副反应及相关基因的多态性研究

摘要

Objective To investigate the relationship of OPRM1 C354A mutations with the clinical efficacy and toxicity of Morphine in the treatment of cancer pain.Methods We recruited 100 patients with moderate-severe cancer pain treated at our department from January 2016 to December 2016,and divided them into a CA(wild type homozygotes) group,a CG(mutated heterozygotes) group,and a GG (homozygous homozygous) group,according to the allele type of OPRM1 C354A.Regular analgesic doses of Morphine were given to all groups,and VAS scores and adverse reactions at 2,4,8,16,24,aud 48 hours after analgesia were collected and compared among the groups.Results The (OPRM1 C354A mutation groups(CG+GG)had lower VAS scores at every time point,compared with those of the non-mutation group(CA) (2 h:3.61±0.39 vs.4.04±0.52;4 h:3.88±0.41 vs.4.20± 0.15;8 h:3.95±0.32 vs.4.37±0.24;16 h:3.81±0.38 vs.4.33±0.15;24 h:3.84±0.25 vs.4.42± 0.18;and48 h:3.86±0.20 vs.4.41± 0.14) (t=4.648,5.261,7.461,8.454,13.389,and 16.030,respectively,each P=0.000).The incidences of constipation(23.08％ vs.6.25％)and vertigo(25％ vs.8.33％)in the OPRM1 C354A mutation groups(CG+GG)were significantly higher than those in the non-mutation group(CA) (x2 =5.543 and 4.914.P=0.019 and 0.027,respectively).Conclusions Polymorphism of the (PRM1 C354A gene is associated with the clinical efficacy and toxicity of morphine in the treatment of cancer pain.%目的 探讨μ阿片受体(OPRM1)C354A位点基因突变与吗啡在癌痛治疗中临床疗效和毒副反应的相关性. 方法 选取2016年1月至2016年12月在我院肿瘤科收治的100例中重度癌痛患者,根据OPRM1 C354A的不同等位基因型分为CA(野生型纯合子)、CG(突变杂合子)和GG组(突变型纯合子),三组患者均予以常规吗啡剂量镇痛,并比较不同基因型患者镇痛后2、4、8、16、24和48 h视觉模拟疼痛(VAS)评分和不良反应发生情况. 结果 OPRM1 C354A突变组(CG+GG)患者镇痛后2 h[(4.04±0.52)分和(3.61±0.39)分]、4 h[(4.20±0.15)分和(3.88±0.41)分]、8 h[(4.37±0.24)分和(3.95±0.32)分]、16 h[(4.33±0.22)分和(3.81±0.38)分]、24 h[(4.42±0.18)分和(3.84±0.25)分]和48 h[(4.41±0.14)分和(3.86±0.20)分)]各个时间点疼痛VAS评分低于未突变组(CA)(t=4.648、5.261、7.461、8.454、13.389和16.030,均P=0.000);OPRM1C354A突变组(CG+GG)组患者便秘(23.08％和6.25％)和眩晕(25.00％和8.33％)等不良反应发生率高于未突变组(x2=5.543和4.914,P=0.019和0.027). 结论 OPRM1 C354A基因多态性与吗啡在癌痛治疗中临床疗效和毒副反应具有相关性.