The polymorphisms can predict the adverse effects of chemotherapy in patients with colorectal cancer

2008 Fiscal Year Final Research Report

• Project/Area Number: 19591545
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Yamaguchi University
• Principal Investigator: HAZAMA Shoichi Yamaguchi University, 大学院・医学系研究科, 准教授 (50253159)
• Co-Investigator(Kenkyū-buntansha): OKAYAMA Naoko 山口大学, 医学部附属病院, 副臨床・衛生検査技師長 (40420541) ; SAKAMOTO Kazuhiko 山口大学, 医学部附属病院, 助教 (50420526)
• Project Period (FY): 2007 – 2008
• Keywords: 大腸癌 / 化学療法 / 遺伝子多型 / 毒性 / UGT1Ai / イリノテカン

Research Abstract

イリノテカンを含む大腸癌化学療法の第I相試験を行い、イリノテカンの推奨投与量をUGT1A1^*28遺伝子型別に決定した。推奨投与量に基づき、第II相試験を行った。その結果、^*28の有無に関わらず、約30%の強い毒性を認めた。ここで毒性の出た患者と毒性の出なかった患者の遺伝子多型を、さらに詳細に検討した結果、UGT1A1^*6, UGT1A7^*3,UGT1A9^*22の遺伝子型が毒性発現に関わっていることが判明した。これらの遺伝子多型を組み合わせて毒性を予測する判別式を作成、またこれら多くの遺伝子多型を判別するチップを開発し、現在両者ともに特許申請中である。

Research Products

• [Journal Article] UGT1A1 *6 is a predictive marker of severe neutropenia for metastatic CRC patients received FOLFIRI in JAPAN (2008)
  • Author(s): S. Hazama, Y. Okuyama, T. Kato, K. Takahashi, H. Nozawa, N. Okayama, Y. Hinoda, M. Oka, J. Sakamoto, H. Mishima
  • Journal Title: Annals of Oncology 19 Pages: Viii138
  • Peer Reviewed
• [Journal Article] CPT-11 (Irinotecan) Gan To Kagaku Ryoho (2008)
  • Author(s): Hazama S, Oka M
  • Journal Title: 35 182 Pages: 182-184
• [Journal Article] 切除不能・再発大腸癌に対するスタンダード化学療法われわれが行っているsequential chemotherapyの工夫 (2008)
  • Author(s): 硲彰一, 長島淳, 近藤浩史, 飯田通久, 吉田晋, 徳久善弘, 蘓村秀明, 友近忍, 岡正朗
  • Journal Title: 癌の臨床 54 Pages: 741-745
• [Journal Article] UGT1As polymorphisms predict toxicity in colorectal cancer patients treated with different recommended doses of irinotecan oriented by UGT1A1*28 polymorphism based on previous phase I study (2007)
  • Author(s): S. Hazama, H. Kondo, S. Yoshida, R. Shimizu, H. Ozasa, T. Yamamoto, A. Araki, S. Yoshino, N. Okayama, Y. Hinoda, M. Oka
  • Journal Title: Journal of Clinical Oncology 25 Pages: 14511
  • Peer Reviewed
• [Presentation] UGT1A1 *6 is a predictive marker of severe neutropenia for metastatic CRC patients received FOLFIRI in JAPAN (2008)
  • Author(s): S. Hazama, Y. Okuyama, T. Kato, K. Takahashi, H. Nozawa, N. Okayama, Y. Hinoda, M. Oka, J. Sakamoto, H. Mishima
  • Organizer: The 33rd ESMO (European society of medical oncology) Congress
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 20080912-16
• [Presentation] UGT1As polymorphisms predict toxicity in colorectal cancer patients treated with different recommended doses of irinotecan oriented by UGT1A1*28 polymorphism based on previous phase I study (2007)
  • Author(s): S. Hazama, H. Kondo, S. Yoshida, R. Shimizu, H. Ozasa, T. Yamamoto, A. Araki, S. Yoshino, N. Okayama, Y. Hinoda, M. Oka
  • Organizer: 2007 ASCO Annual Meeting
  • Place of Presentation: Chicago/IL/USA
  • Year and Date: 20070601-05
• [Patent(Industrial Property Rights)] 薬剤の作用・副作用予測システムとそのプログラム (2008)
  • Inventor(s): 硲彰一、他
  • Industrial Property Rights Holder: 硲彰一、他
  • Industrial Property Number: 特願,2008-306916
  • Filing Date: 2008-12-01