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. 2017 Oct;7(4):380-384.
doi: 10.3892/br.2017.963. Epub 2017 Aug 8.

Prospective replication study implicates the catechol-O-methyltransferase Val158Met polymorphism as a biomarker for the response to morphine in patients with cancer

Hiromichi Matsuoka  1   2 , Chihiro Makimura  1 , Atsuko Koyama  1 , Yoshihiko Fujita  3 , Junji Tsurutani  4 , Kiyohiro Sakai  1 , Ryo Sakamoto  1 , Kazuto Nishio  3 , Kazuhiko Nakagawa  4
Affiliations

Prospective replication study implicates the catechol-O-methyltransferase Val158Met polymorphism as a biomarker for the response to morphine in patients with cancer

Hiromichi Matsuoka et al. Biomed Rep. 2017 Oct.

Abstract

Genetic differences in humans cause clinical difficulties in opioid treatment. Previous studies indicate that a single nucleotide polymorphism in the catechol-O-methyltransferase (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-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.

Keywords: biomarker; cancer; catechol-O-methyltransferase polymorphism; morphine; pain; replication study.

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Figures

Figure 1.
Figure 1.
Schema of the study design. NSAIDs, non-steroidal anti-inflammatory drugs; NRS, numerical rating scale; SNPs, single nucleotide polymorphisms; COMT, catechol-O-methyltransferase.
Figure 2.
Figure 2.
Genotypes were evaluated for COMT 472G→A (rs4680; p.Val158Met). The treatment outcome of morphine was examined based on the required dose (day 1). Comparisons are for G/G vs. A/A and A/G of COMT. The P-value was calculated using a Mann-Whitney U test. COMT, catechol-O-methyltransferase.
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