Source:http://linkedlifedata.com/resource/pubmed/id/17185998
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2006-12-22
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pubmed:abstractText |
Interindividual pharmacokinetic variability of the anticancer agent irinotecan is high. Life-threatening diarrhea is observed in up to 25% of patients receiving irinotecan and has been related with irinotecan pharmacokinetics and UGT1A1 genotype status. Here, we explore the association of ABCC2 (MRP2) polymorphisms and haplotypes with irinotecan disposition and diarrhea. A cohort of 167 Caucasian cancer patients who were previously assessed for irinotecan pharmacokinetics (90-min infusion given every 21 days), toxicity, and UGT1A1*28 genotype were genotyped for polymorphisms in ABCC2 using Pyrosequencing. Fifteen ABCC2 haplotypes were identified in the studied patients. The haplotype ABCC2*2 was associated with lower irinotecan clearance (28.3 versus 31.6 l/h; P=0.020). In patients who did not carry a UGT1A1*28 allele, a significant reduction of severe diarrhea was noted in patients with the ABCC2*2 haplotype (10 versus 44%; odds ratio, 0.15; 95% confidence interval, 0.04-0.61; P=0.005). This effect was not observed in patients with at least one UGT1A1*28 allele (32 versus 20%; odds ratio, 1.87; 95% confidence interval, 0.49-7.05; P=0.354). This study suggests that the presence of the ABCC2*2 haplotype is associated with less irinotecan-related diarrhea, maybe as a consequence of reduced hepatobiliary secretion of irinotecan. As the association was seen in patients not genetically predisposed at risk for diarrhea due to UGT1A1*28, confirmatory studies of the relationships of ABCC2 genotypes and irinotecan disposition and toxicity are warranted.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Glucuronosyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Multidrug Resistance-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/bilirubin...,
http://linkedlifedata.com/resource/pubmed/chemical/irinotecan,
http://linkedlifedata.com/resource/pubmed/chemical/multidrug resistance-associated...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0009-9236
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
42-9
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17185998-Adult,
pubmed-meshheading:17185998-Aged,
pubmed-meshheading:17185998-Alleles,
pubmed-meshheading:17185998-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:17185998-Camptothecin,
pubmed-meshheading:17185998-Diarrhea,
pubmed-meshheading:17185998-Female,
pubmed-meshheading:17185998-Glucuronosyltransferase,
pubmed-meshheading:17185998-Humans,
pubmed-meshheading:17185998-Male,
pubmed-meshheading:17185998-Membrane Transport Proteins,
pubmed-meshheading:17185998-Middle Aged,
pubmed-meshheading:17185998-Multidrug Resistance-Associated Proteins,
pubmed-meshheading:17185998-Polymorphism, Single Nucleotide
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pubmed:year |
2007
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pubmed:articleTitle |
Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2 transporter protein.
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pubmed:affiliation |
Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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