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THE ROLE OF GENETIC POLYMORPHISMS OF DRUG TRANSPORTER GENES FOR THE TREATMENT OF LUNG CANCER

Research Project

Project/Area Number 17590786
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNAGOYA UNIVERSITY

Principal Investigator

HASEGAWA Yoshinori  UNIVERSITY HOSPITAL, ASSOCIATE PROFESSOR, 医学部附属病院, 講師 (20270986)

Co-Investigator(Kenkyū-buntansha) IMAIZUMI Kazuyoshi  UNIVERSITY HOSPITAL, ASSOCIATE PROFESSOR, 医学部附属病院, 講師 (50362257)
KAWABE Tsutomu  NAGOYA UNIVERSITY, SCHOOL OF MEDICINE, RESEARCH ASSOCIATE, 医学部, 助手 (20378219)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsIrinotecan / ABC transporters / gene polymorphisms / ABCC2 / OATP-C / UGT1A1^*28 / UGT1A1*28 / ABCG2
Research Abstract

Irinotecan unexpectedly causes severe, occasionally fatal, toxicity of leukopenia or diarrhea. Adenosine triphosphate-binding cassette transporters (ABCC2) transport irinotecan and its metabolites from hepatocytes to the bile. We assessed whether variant forms of ABCC2 would affect inter-patient variations in sensitivity to irinotecan toxicity in 120 Japanese patients with a cancer. The genotyping of ABCC2 was performed by direct sequencing of the PCR fragment. We found five polymorphisms in ABCC2. ABCC2 2375A>G is a new polymorphism, substituting aspartic acid for glycine. Univariate logistic regression analysis found no significant association between severe toxicities and carrying at ABCC2 polymorphisms. The results suggested that the determination of nucleic polymorphisms of ABCC2 would not be useful for predicting severe toxicities by irinotecan. On the other hand, organic anion transporting polypeptide C (OATP-C) plays a major role in the transport of SN-38 from portal venous blood to hepartocytes. The allele frequencies of OATP-C^*1 a, OATP-C^*1b, and OATP-C^*15 were 0.31, 0.58, and 0.11, respectively. Logistic regression analysis did not show any significant association between the occurrence of severe toxicity and carrying OATP-C^*15. The double variants for OATP-C^*15 and UGT1A1 ^*28 tended to be associated with the occurrence of severe toxicity, although it was not statistically significant.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (20 results)

All 2006 2005

All Journal Article (20 results)

  • [Journal Article] Pharmacogenetic approach for cancer treatment -Tailored medicine in practice-2006

    • Author(s)
      Hasegawa Y, et al.
    • Journal Title

      Ann NY Acad Sci 1086

      Pages: 223-232

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Screening for adverse reactions to irinotecantreatment using the Invader UGT1A1 Molecular Assay2006

    • Author(s)
      Hasegawa Y, et al.
    • Journal Title

      Expert Review of Molecular Diagnostics. 6

      Pages: 527-533

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer.2006

    • Author(s)
      Suzuki R, Hasegawa Y, et al.
    • Journal Title

      Brit J Cancer 94

      Pages: 1599-1603

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Expression of macrophage-derived chemokine (MDC)/CCL22 in human lung cancer.2006

    • Author(s)
      Nakanishi T, Hasegawa Y, et al.
    • Journal Title

      Cancer Immunol Immunother 55

      Pages: 1320-1329

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] EGFR point mutation in non-small cell lung cancer is occasionally accompanied by a second mutation or amplification2006

    • Author(s)
      Yokoyama T, Hasegawa Y, et al.
    • Journal Title

      Cancer Sci 97

      Pages: 753-759

    • NAID

      10018768298

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Successful re-treatment with gefitinib for carcinomatous meningitis as disease recurrence of non-small-cell lung cancer2006

    • Author(s)
      Hashimoto N, Hasegawa Y et al.
    • Journal Title

      Lung Cancer 53

      Pages: 387-390

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Pharmacogenetic approach for cancer treatment -Tailored medicine in practice-2006

    • Author(s)
      Hasegawa Y, Ando Y, Ando M, Hashimoto N, Imaizumi K, Shimokata K.
    • Journal Title

      Ann NY Acad Sci 1086

      Pages: 223-232

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Screening for adverse reactions to irinotecan treatment using the Invader UGT1A1 Molecular Assay.2006

    • Author(s)
      Hasegawa Y, Ando Y, Shimokata K.
    • Journal Title

      Expert Review of Molecular Diagnostics 6

      Pages: 527-533

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer.2006

    • Author(s)
      Suzuki R, Hasegawa Y, Baba K, Saka H, Saito H, Taniguchi H, Yamamoto M, Matsumoto S, Kato K, Oishi T, Imaizumi K, Shimokata K.
    • Journal Title

      British Journal of Cancer 94

      Pages: 1599-1603

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of macrophage-derived chemokine (MDC)/CCL22 in human lung cancer.2006

    • Author(s)
      Nakanishi T, Imaizumi K, Hasegawa Y, Kawabe T, Hashimoto N, Okamoto M, Shimokata K.
    • Journal Title

      Cancer Immunology Immunotherapy 55

      Pages: 1320-1329

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] EGFR point mutation in non-small cell lung cancer is occasionally accompanied by a second mutation or amplification.2006

    • Author(s)
      Yokoyama T, Kondo M, Goto Y, Fukui T, Yoshioka H, Yokoi K, Osada H, Imaizumi K, Hasegawa Y, Shimokata K, Sekido Y.
    • Journal Title

      Cancer Science 97

      Pages: 753-759

    • NAID

      10018768298

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Successful re-treatment with gefitinib for carcinomatous meningitis as disease recurrence of non-small-cell lung cancer.2006

    • Author(s)
      Hashimoto N, Imaizumi K, Honda T, Kawabe T, Nagasaka T, Shimokata K, Hasegawa Y.
    • Journal Title

      Lung Cancer 53

      Pages: 387-390

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pharmacogenetic approach for cancer treatment-Tailored medicine in practive-2006

    • Author(s)
      Hasegawa Y, et al.
    • Journal Title

      Ann NY Acad Sci 1086

      Pages: 223-232

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Screening for adverse reactions to irinotecantreatment using the Invader UGT1A1 Molecular Assay2006

    • Author(s)
      Hasegawa Y, et al.
    • Journal Title

      Expert Review of Molecular Diagnostics 6

      Pages: 527-533

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mutation of epidermal growth factor receptor of non-small cell lung cancer were associated with sensitivity to gefitinib in recurrence after surgery.2005

    • Author(s)
      Kondo M, Yokoyama T, Fukui T, et al.
    • Journal Title

      Lung Cancer 50

      Pages: 385-391

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Pharmacogenetics of iriotecan : a promoter polymorphism of UGT1A1 gene and severe adverse reactions to irinotecan.2005

    • Author(s)
      Ando M, Hasegawa Y, Ando Y.
    • Journal Title

      Investigational New Drugs 23

      Pages: 539-545

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinical pharmacogenetics of irinotecan(CPT-11).2005

    • Author(s)
      Ando Y, Hasegawa Y.
    • Journal Title

      Drug Metabolism Reviews 37

      Pages: 565-574

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Irinotecan therapy in a 12-years-old girl with recurrent brain stem glioma and without functional polymorphisms in UGT1A1 activity : case report.2005

    • Author(s)
      Shikawa K, Kajita Y, Hasegawa Y, et al.
    • Journal Title

      Journal of Neuro-Oncology 74

      Pages: 283-286

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Genetic polymorphism in the phenobarbital-responsive enhancer module of the UDP-glucuronosyltransferase 1A1 gene and irinotecan toxicity.2005

    • Author(s)
      Kitagawa C, Ando M, Ando Y, et al.
    • Journal Title

      Pharmacogenetics and Genomics 15

      Pages: 35-41

    • Related Report
      2005 Annual Research Report
  • [Journal Article] T-helper type 1/T-helper type 2 balance in malignant pleural effusions compared to tuberculous pleural effusions.2005

    • Author(s)
      Okamoto M, Hasegawa Y, Hara T, et al.
    • Journal Title

      Chest 128

      Pages: 4030-4035

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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