講演情報
[P28-3]がん性疼痛治療におけるオピオイド鎮痛薬必要量のゲノムワイド解析
○西澤 大輔1, 照井 健2, 石谷 邦彦2, 笠井 慎也1, 長谷川 準子1, 中山 京子1, 江畑 裕子1, 池田 和隆1 (1.東京都医学総合研究所 精神行動医学研究分野（依存性物質プロジェクト）, 2.東札幌病院 診療部 内科)
Purpose: Considerable individual differences have been widely observed in sensitivity to opioid analgesics. We conducted a genome-wide association study (GWAS) in patients with cancer pain to identify potential candidate single nucleotide polymorphisms (SNPs) that may significantly contribute to individual differences in opioid analgesic requirements in the pain treatment. Methods: The subjects in the association study were a total of 428 patients with written informed consent who underwent treatment of pain with opioid analgesics at palliative care unit of Higashi-Sapporo Hospital. The study protocol was approved by the Institutional Review Board at each related institute. Total genomic DNA was extracted from peripheral blood samples and genotyping was conducted using whole-genome genotyping arrays with more than 650,000 markers. Results: As a result of GWAS in cancer pain patients, two intronic SNPs in the ANGPT1 gene region, rs1283671 and rs1283720, were strongly associated with opioid requirements per day for the treatment of pain in additive and recessive models (P ＜ 5.0000 × 10-8) and several other SNPs were also significantly associated with the phenotype. The T allele of this best-candidate SNP, rs1283671, was associated with greater opioid requirements. Conclusions: The results indicate that the rs1283671 SNP could serve as a marker that predicts analgesic requirements, in which the T allele of this SNP is associated with increased requirement of opioid analgesics. Our findings will provide valuable information for achieving satisfactory cancer pain control.