ABCB1, SLCO1B1 and UGT1A1 Gene Polymorphisms Are Associated with Toxicity Line Irinotecan

Authors: Rhodes, Katrin E.¹; Zhang, Wu¹; Yang, Dongyun¹; Press, Oliver A.¹; Gordon, Michael¹; Vallbohmer, Daniel¹; Schultheis, Anne M.¹; Lurje, Georg¹; Ladner, Robert D.¹; Fazzone, William¹; Lenz, Heinz-Josef¹; Iqbal, Syma¹

Source: Drug Metabolism Letters, Volume 1, Number 1, January 2007 , pp. 23-30(8)

Publisher: Bentham Science Publishers

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Drug Metabolism Letters publishes short papers on major advances in all areas of drug metabolism and disposition. The emphasis will be on publishing quality papers very rapidly. Letters will be processed rapidly by taking full advantage of the Internet technology for both the submission and review of manuscripts. The journal covers the following areas:

In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites, reactive intermediate and glutathione conjugates.

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By this author: Rhodes, Katrin E. ; Zhang, Wu ; Yang, Dongyun ; Press, Oliver A. ; Gordon, Michael ; Vallbohmer, Daniel ; Schultheis, Anne M. ; Lurje, Georg ; Ladner, Robert D. ; Fazzone, William ; Lenz, Heinz-Josef ; Iqbal, Syma

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Abstract:

We tested specific gene polymorphisms known to be involved in the irinotecan (CPT-11) metabolic pathway. The combination of at least one SLCO1B1 521 T allele, one ABCB1 1236 C allele and one UGT1A1*28 variant 7 repeat demonstrated a statistically significant association with Grade 3/4 toxicities in metastatic colorectal cancer patients.

Keywords: Polymorphisms; colorectal cancer; toxicity; irinotecan

Document Type: Research article

DOI: 10.2174/187231207779814328

Affiliations: 1: Oncology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Avenue, Suite 3456, Los Angeles, CA 90033, USA.