National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China.
Cancer. 2012 Mar 15;118(6):1718-25. doi: 10.1002/cncr.26430. Epub 2011 Aug 11.
The A118G polymorphism of the mu-opioid receptor gene (OPRM1), resulting in the substitution of an amino acid, has been found to be associated with functional effects and response to opioid treatment. The purpose of this study was to assess whether this polymorphism contributes to the variability in response to tramadol/acetaminophen combination tablets (Ultracet) for treating oxaliplatin-induced painful neuropathy.
A total of 96 patients with adenocarcinoma of the colon or rectum (n = 84), or stomach (n = 12) who had developed oxaliplatin-induced painful neuropathy were enrolled. Ultracet was administered at 1 tablet every 6 hours, and pain was assessed and scored using a visual analog scale (VAS). The OPRM1 A118G polymorphism was examined with a polymerase chain reaction-direct sequencing method.
The allelic frequency of variant (118G) allele was 39.6%, and the prevalence of OPRM1-118 AA, AG, and GG genotypes was 31.3% (n = 30), 58.3% (n = 56), and 10.4% (n = 10), respectively. For all patients, the mean pre-treatment and post-treatment VAS scores were 3.1 and 2.1, respectively (P < .001). Patients with AA genotype had a better analgesic effect than those with G allele variants (AG or GG genotypes). Pre-treatment and post-treatment VAS scores for patients with G allele variants were 3.1 and 2.6, respectively; however, for patients with AA genotype, pre-treatment and post-treatment VAS scores were 3.0 and 0.9, respectively (P < .001). The requirement for rescue analgesia was also higher for patients with G allele variants (P = .01).
These data suggest that Ultracet is effective in the management of oxaliplatin-induced painful neuropathy. A118G polymorphism of OPRM1, by altered function of the mu-opioid receptor and consequential analgesic effect on opioid agents, could be a key determinant for decreased response to Ultracet.
μ-阿片受体基因（OPRM1）的 A118G 多态性导致氨基酸替换，已被发现与功能影响和阿片类药物治疗反应相关。本研究旨在评估该多态性是否导致曲马多/对乙酰氨基酚复方片剂（优泰）治疗奥沙利铂诱导的痛性神经病的反应存在差异。
共纳入 96 例患有结肠或直肠腺癌（n=84）或胃癌（n=12）且发生奥沙利铂诱导的痛性神经病的患者。给予优泰，每 6 小时 1 片，使用视觉模拟评分法（VAS）评估疼痛并评分。采用聚合酶链反应-直接测序法检测 OPRM1 A118G 多态性。
变异（118G）等位基因的等位基因频率为 39.6%，OPRM1-118AA、AG 和 GG 基因型的患病率分别为 31.3%（n=30）、58.3%（n=56）和 10.4%（n=10）。所有患者的平均治疗前和治疗后 VAS 评分分别为 3.1 和 2.1（P<0.001）。AA 基因型患者的镇痛效果优于携带 G 等位基因变异（AG 或 GG 基因型）的患者。携带 G 等位基因变异的患者治疗前和治疗后 VAS 评分分别为 3.1 和 2.6，而 AA 基因型患者的 VAS 评分分别为 3.0 和 0.9（P<0.001）。携带 G 等位基因变异的患者对解救性镇痛的需求也更高（P=0.01）。
这些数据表明，优泰对奥沙利铂诱导的痛性神经病的治疗有效。OPRM1 的 A118G 多态性通过改变μ-阿片受体的功能和对阿片类药物的镇痛作用，可能是导致对优泰反应降低的关键决定因素。
