Genetic research on mechanisms of opioid system and carcinoma

• 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
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 麻薬性鎮痛薬 / 痛み / 癌 / 遺伝子 / 遺伝多型 / 内因性オピオイド / 疼痛管理 / オピオイド / がん

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.

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。

Research Products

• [Presentation] Effect of receptor polymorphism on the risk factor for breast cancer in Japanese (2019)
  • Author(s): Shinichi Inomata， Maiko Ishigaki
  • Organizer: Euroanaesthesia 2019
  • Int'l Joint Research
• [Presentation] オピオイド受容体遺伝子変異は日本人における乳癌の危険因子となるか (2019)
  • Author(s): 猪股伸一
  • Organizer: 日本麻酔科学会総会
• [Presentation] Effect of opioid receptor polymorphism on the risk factor for breast cancer in Japanese (2018)
  • Author(s): Inomata S, Ishigaki M.
  • Organizer: Euroanaesthesia 2018, The Europian Anaesthesiology Congress
  • Int'l Joint Research