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Genetic polymorphisms to analyze and predict treatment-related adverse effects in children with acute lymphoblastic leukemia

Research Project

Project/Area Number 20790135
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionKobe University

Principal Investigator

NAKAMURA Tsutomu  Kobe University, 薬学部, 教授 (80379411)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsオーダーメード医療 / 小児白血病 / 遺伝子多型
Research Abstract

Some children with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) experience clinically important treatment-related adverse effects. In the present study, to identify novel potential loci influencing the risk of treatment-related hepatotoxicity during the maintenance phase, a genome-wide genotyping analysis was performed in Japanese children with ALL or LBL. Genome-wide genotyping uncovered a total of 28 candidate SNPs. rs1966862, in Rho GTPase-activating protein 24 (ARHGAP24), was the most significant of the candidates, and the genotypes of rs7403531 (RASGRP1) and some genes were also significantly associated with severe hepatotoxicity. This study suggested rs1966862 (ARHGAP24) and the other SNPs to be predictive factors for drug-induced hepatotoxicity during the maintenance phase in pediatric patients with ALL or LBL.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (22 results)

All 2011 2010 2009 2008

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (7 results) Book (1 results)

  • [Journal Article] VEGF 936C>T is Predictive of Threshold Retinopathy of Prematurity in Japanese Infants with a 30 weeks Gestational age or less.2011

    • Author(s)
      M.Yagi, T.Nakamura, 他
    • Journal Title

      Res Rep Neonatol. volume 1

      Pages: 5-11

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] VEGF 936C>T is Predictive of Threshold Retinopathy of Prematurity in Japanese Infants with a 30 weeks Gestational age or less.2011

    • Author(s)
      Mariko Yagi
    • Journal Title

      Res Rep Neonatol.

      Volume: 1 Pages: 5-11

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of dose-escalation of 5-fluorouracil on circadian variability of its pharmacokinetics in Japanese patients with Stage III/IVa esophageal squamous cell carcinoma.2010

    • Author(s)
      A.Kuwahara, T.Nakamura, 他
    • Journal Title

      Int J Med Sci. volume 7

      Pages: 48-54

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carci-noma.2010

    • Author(s)
      A.Kuwahara, T.Nakamura, 他
    • Journal Title

      J Exp Clin Cancer Res. volume 29

      Pages: 100-100

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Association of Genetic Polymorphisms with Hepatotoxicity in Patients with Childhood Acute Lymphoblastic Leukemia or Lymphoma.2010

    • Author(s)
      M.Horinouchi, T.Nakamura, 他
    • Journal Title

      Pediatr Hematol Oncol. volume 27

      Pages: 344-354

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of CPS14217C>A genotype on valproic acid-induced hyperammonemia.2010

    • Author(s)
      M.Yagi, T.Nakamura, 他
    • Journal Title

      Pediatr Int. volume 52

      Pages: 744-748

    • NAID

      10028184232

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma.2010

    • Author(s)
      Akiko Kuwahara
    • Journal Title

      J Exp Clin Cancer Res.

      Volume: 29 Pages: 100-100

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of Genetic Polymorphisms with Hepatotoxicity in Patients with Childhood Acute Lymphoblastic Leukemia or Lymphoma.2010

    • Author(s)
      Masanori Horinouchi
    • Journal Title

      Pediatr Hematol Oncol.

      Volume: 27 Pages: 344-354

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of CPS1 4217C>A genotype on valproic acid-induced hyperammonemia.2010

    • Author(s)
      Mariko Yagi
    • Journal Title

      Pediatr Int.

      Volume: 52 Pages: 744-748

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of dose-escalation of 5-fluorouracil on circadian variability of its pharmacokinetics in Japanese patients with Stage III/IVa esophageal squamous cell carcinoma2010

    • Author(s)
      Akiko Kuwahara
    • Journal Title

      Int J Med Sci. 7

      Pages: 48-54

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of ABCB1 3435C>T genotype on serum levels of cortisol and aldosterone in women with normal menstrual cycles.2009

    • Author(s)
      T.Nakamura, 他
    • Journal Title

      Genet Mol Res. volume 8

      Pages: 397-403

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Replacement of cisplatin with nedaplatin in a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma.2009

    • Author(s)
      A.Kuwahara, T.Nakamura, 他
    • Journal Title

      Int J Med Sci. volume 6

      Pages: 305-311

    • NAID

      120001887679

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of ABCB1 3435C>T genotype on serum levels of cortisol and aldosterone in women with normal menstrual cycles2009

    • Author(s)
      Tsutomu Nakamura
    • Journal Title

      Genet Mol Res. 8

      Pages: 397-403

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Replacement of cisplatin with nedaplatin in a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma2009

    • Author(s)
      Akiko Kuwahara
    • Journal Title

      Int J Med Sci. 6

      Pages: 305-311

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Effects of acid and lactone forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on the induction of MDR1 expression and function in LS180 cells.2009

    • Author(s)
      D.Yamasaki, T.Nakamura, 他
    • Organizer
      日本薬物動態学会第24回年会
    • Place of Presentation
      京都・京都国際会館
    • Year and Date
      2009-11-27
    • Related Report
      2010 Final Research Report
  • [Presentation] Effects of acid and lactone forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on the induction of MDR1 expression and function in LS180 cells2009

    • Author(s)
      Daisuke Yamasaki
    • Organizer
      日本薬物動態学会第24回年会
    • Place of Presentation
      京都・国立京都国際会館
    • Year and Date
      2009-11-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] 食道癌化学放射線療法における患者個別化への取り組み2009

    • Author(s)
      中村任
    • Organizer
      第6回九州山口薬学会ファーマシューティカルケアシンポジウム
    • Place of Presentation
      熊本・崇城大学市民ホール.
    • Year and Date
      2009-02-15
    • Related Report
      2010 Final Research Report
  • [Presentation] Genetic polymorphisms associated with hepatotoxicity in patients with Japanese childhood leukemia.2008

    • Author(s)
      M.Horinouchi, T.Nakamura, 他
    • Organizer
      第2回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      京都・京都大学薬学部.
    • Year and Date
      2008-12-21
    • Related Report
      2010 Final Research Report
  • [Presentation] Genetic polymorphisms associated with hepatotoxicity in patients with Japanese childhood leukemia2008

    • Author(s)
      Masanori Horinouchi
    • Organizer
      第2回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      京都・京都大学薬学部
    • Year and Date
      2008-12-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] 小児リンパ性白血病患者における肝障害発現関連SNP の網羅的探索2008

    • Author(s)
      堀之内正則, 中村任, 他
    • Organizer
      第29回日本臨床薬理学会年会
    • Place of Presentation
      東京・京王プラザホテル
    • Year and Date
      2008-12-06
    • Related Report
      2010 Final Research Report
  • [Presentation] 小児リンパ性白血病患者における肝障害発現関連SNPの網羅的探索2008

    • Author(s)
      堀之内正則
    • Organizer
      第29回日本臨床薬理学会年会
    • Place of Presentation
      東京・京王プラザホテル
    • Year and Date
      2008-12-06
    • Related Report
      2008 Annual Research Report
  • [Book] 製剤学・物理薬剤学(柴崎正勝, 赤池昭紀, 橋田充 監修, 栄田敏之, 唐澤健, 岡本浩一 編集)2009

    • Author(s)
      中村任, 他
    • Publisher
      廣川書店
    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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