Matsuoka Hiromichi, Makimura Chihiro, Koyama Atsuko, Fujita Yoshihiko, Tsurutani Junji, Sakai Kiyohiro, Sakamoto Ryo, Nishio Kazuto, Nakagawa Kazuhiko
Department of Psychosomatic Medicine, Kindai University Faculty of Medicine, Osaka 589-8511, Japan.
Department of Palliative Care Center, Kindai University Faculty of Medicine, Osaka 589-8511, Japan.
Biomed Rep. 2017 Oct;7(4):380-384. doi: 10.3892/br.2017.963. Epub 2017 Aug 8.
Genetic differences in humans cause clinical difficulties in opioid treatment. Previous studies indicate that a single nucleotide polymorphism in the catechol-O-methyltransferase () gene (rs4680; p.ValMet) 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-naïve 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 naïve 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.
人类的基因差异导致阿片类药物治疗出现临床难题。先前的研究表明，儿茶酚-O-甲基转移酶（COMT）基因中的单核苷酸多态性（rs4680；p.Val158Met）可能作为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基因型的患者相比，G/G基因型的患者被证明需要更高剂量的吗啡。在本研究中，目的是在一组独立的初治阿片类药物治疗的患有各种癌症的患者中重复这些发现。这项前瞻性研究于2011年至2012年在近畿大学医学院进行。本研究共评估了50例初治阿片类药物且经组织学确诊为恶性肿瘤并计划接受阿片类药物治疗的患者。在治疗前（第1天）、治疗后（第1天）和治疗后一周（第8天）进行评估。与A/A和A/G基因型的患者相比，COMT基因G/G基因型的患者在第1天所需的吗啡剂量显著更高（P=0.013）。本研究结果提供了额外的证据，表明COMT基因型可能是吗啡治疗反应的预测生物标志物。
