Prospective replication study implicates the catechol-O-methyltransferase Val158Met polymorphism as a biomarker for the response to morphine in patients with cancer
Prospective replication study implicates the catechol-O-methyltransferase Val158Met polymorphism as a biomarker for the response to morphine in patients with cancer
复制标题
DOI：
10.3892/br.2017.963
复制
发表时间：
2017-10-01
影响因子：
2.3
通讯作者：
Nakagawa, Kazuhiko
中科院分区：
文献类型：
--
作者：
Matsuoka, Hiromichi;Makimura, Chihiro;Nakagawa, Kazuhiko
人类的遗传差异导致阿片类药物治疗的临床困难。先前的研究表明，儿茶酚O-甲基转移酶（COMT）基因（rs 4680; p.Val158Met）中的单核苷酸多态性可能是吗啡治疗反应的预测生物标志物。在我们之前的初步探索性研究中，与A/A和A/G基因型患者相比，G/G基因型患者需要更高剂量的吗啡。在本研究中，目的是在表现出各种类型癌症的阿片类药物治疗初治患者的独立队列中复制这些发现。这项前瞻性研究于2011年至2012年在Kindai大学医学部进行。本研究共评价了50例阿片类药物初治和组织学证实的恶性肿瘤患者，这些患者计划接受阿片类药物治疗。在治疗前（第1天）、治疗后（第1天）和治疗后1周（第8天）进行评估。与A/A和A/G基因型患者相比，COMT基因G/G基因型患者第1天所需吗啡剂量显著增加（P=0.013）。本研究的结果提供了额外的证据表明，COMT基因型可能是一个预测生物标志物的吗啡治疗的反应。
Genetic differences in humans cause clinical difficulties in opioid treatment. Previous studies indicate that a single nucleotide polymorphism in the catecholO-methyl-transferase (COMT) gene (rs4680; p. Val158Met) may present as a predictive biomarker for the response to morphine treatment. In our previous pilot exploratory study, patients with a G/G genotype were demonstrated to require a higher dose of morphine, compared with patients with A/A and A/G genotypes. In the present study, the aim was to replicate the findings in an independent cohort of opioid-treatment-naive patients exhibiting various types of cancer. This prospective study was conducted from 2011 to 2012 at the Kindai University Faculty of Medicine. A total of 50 patients with opioid-treatment naive and histologically confirmed malignant neoplasms who were scheduled to undergo opioid treatment were evaluated in the present study. Assessments were conducted pre-treatment (day 1), post-treatment (day 1), and one week after treatment (day 8). The required dose of morphine on day 1 was significantly higher for patients with the G/G genotype of COMT, compared with those with the A/A and A/G genotypes (P=0.013). The results of the present study provide additional evidence that the COMT genotype may be a predictive biomarker for the response to morphine treatment.