Novel single nucleotide polymorphism biomarkers to predict opioid effects for cancer pain

Yoshihiko Fujita; Hiromichi Matsuoka; Yasutaka Chiba; Junji Tsurutani; Takeshi Yoshida; Kiyohiro Sakai; Miki Nakura; Ryo Sakamoto; Chihiro Makimura; Yoichi Ohtake; Kaoru Tanaka; Hidetoshi Hayashi; Masayuki Takeda; Tatsuya Okuno; Naoki Takegawa; Koji Haratani; Takayuki Takahama; Junko Tanizaki; Atsuko Koyama; Kazuto Nishio; Kazuhiko Nakagawa

doi:10.3892/ol.2023.13941

Novel single nucleotide polymorphism biomarkers to predict opioid effects for cancer pain

Oncol Lett. 2023 Jul 4;26(2):355. doi: 10.3892/ol.2023.13941. eCollection 2023 Aug.

Authors

Yoshihiko Fujita¹, Hiromichi Matsuoka^{2

3

4}, Yasutaka Chiba⁵, Junji Tsurutani^{6

7}, Takeshi Yoshida^{2

7}, Kiyohiro Sakai^{2

3}, Miki Nakura², Ryo Sakamoto², Chihiro Makimura², Yoichi Ohtake², Kaoru Tanaka⁷, Hidetoshi Hayashi⁷, Masayuki Takeda⁷, Tatsuya Okuno⁷, Naoki Takegawa⁷, Koji Haratani⁷, Takayuki Takahama⁷, Junko Tanizaki⁷, Atsuko Koyama^{2

3}, Kazuto Nishio¹, Kazuhiko Nakagawa⁷

Affiliations

¹ Department of Genome Biology, Kindai University Faculty of Medicine, Osaka 589-8511, Japan.
² Department of Psychosomatic Medicine, Kindai University Faculty of Medicine, Osaka 589-8511, Japan.
³ Palliative Care Center, Kindai Hospital, Osaka 589-8511, Japan.
⁴ Palliative Care Team, National Cancer Center, Tokyo 104-0045, Japan.
⁵ Department of Biostatics, Kindai University Faculty of Medicine, Osaka 589-8511, Japan.
⁶ Advanced Cancer Translational Research Institute, Showa University, Tokyo 142-8555, Japan.
⁷ Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka 589-8511, Japan.

Abstract

There have been few studies on predictive biomarkers that may be useful to select the most suitable opioids to optimize therapeutic efficacy in individual patients with cancer pain. We recently investigated the efficacy of morphine and oxycodone using single nucleotide polymorphisms (SNPs) of the catechol-O-methyltransferase (COMT) rs4680 gene as a biomarker (RELIEF study). To explore additional biomarkers that may enable the selection of an appropriate opioid for individual patients with cancer pain, three SNPs were examined: C-C motif chemokine ligand 11 (CCL11; rs17809012), histamine N-methyltransferase (HNMT; rs1050891) and transient receptor potential V1 (TRPV1; rs222749), which were screened from 74 pain-related SNPs. These SNPs, which were identified as being significantly associated with the analgesic effect of morphine, were then used to genotype the 135 patients in the RELIEF study who had been randomized into a morphine group (n=69) or an oxycodone group (n=66). The present study then assessed whether the SNPs could also be used as selective biomarkers to predict which opioid(s) might be the most suitable to provide pain relief for patients with cancer. Oxycodone tended to provide superior analgesic effects over morphine in patients carrying the genotype AA for the CCL11 rs17809012 SNP (P=0.012 for interaction), suggesting that it could serve as a potential biomarker for personalized analgesic therapy for patients suffering with cancer pain.

Keywords: CCL11; SNP; cancer pain; genotype; morphine; oxycodone.

Grants and funding

This study was financially supported by the Health Labor Sciences Research Grant (Grant for Innovative Clinical Cancer Research: H26-Innovative Cancer-General-056; grant no. 16ck0106059h0003) and the Japan Agency for Medical Research and Development (Innovative Clinical Cancer Research: grant no. 17ck0106328h0001).