Genetic research on mechanisms of opioid system and carcinoma

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11101
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: University of Tsukuba
• Principal Investigator: SHINICHI INOMATA 筑波大学, 医学医療系, 准教授 (10282352)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 麻薬性鎮痛薬 / 痛み / 癌 / 遺伝子 / 遺伝多型

Outline of Final Research Achievements

Opioid receptors are expressed in breast cancer cells. It has been reported that morphine promotes tumor progression and metastasis. The mu-opioid receptor1 (OPRM1) A118G SNP is frequently discussed in terms of opioid analgesia and affinity with endogenous opioid. There are several research reports on the association between the G allele in the OPRM1 A118G SNP of the opioid receptor and the incidence of breast cancer.
To investigate the cause of discrepancy in research results, a three-group comparison with GG genotype as independent group has not yet been performed due to the low frequency of G allele in Caucasians. We performed a three-group comparison in Japanese women, who have a higher frequency of the mutant. No significant difference was deteted in the distribution of the OPRM1 A118G SNP in Japanese breast cancer patients by the three group comparison of AA/AG/GG genotypes. Further studies should be performed to determine the association between the SNPs and cancer incidence.

Free Research Field

麻酔科学、ペインクリニック、遺伝子解析

Academic Significance and Societal Importance of the Research Achievements

麻薬性鎮痛薬は、術後痛や慢性痛、癌患者の治療に広く利用されている。しかし麻薬性鎮痛薬は癌細胞を分化、癌転移を促進するという報告がある。麻薬性鎮痛薬が作用する受容体には、体内にある麻薬様物質（OP）も作用し、その物質は免疫系も調節する。先ず女性の癌で最多の乳癌に注目し研究を進めた。上記に加えエストロゲン受容体は内因性OPに制御され、OP受容体遺伝子変異が危険因子と考えたのが理由である。
本邦ではhomo変異型（GG）の頻度が多く、これを独立群とした3群比較が可能であり、信頼性の高い結果が得られた。また、海外の研究結果は日本人に当てはまらないことが懸念され、現在多くのSNPについて急ぎ解析している。