Abstract:
AIMS:The current study investigates whether or not functional polymorphisms in the ATP-binding cassette transporter gene ABCG2 might affect gefitinib activity and/or toxicity in non-small-cell lung cancer (NSCLC) patients. MATERIALS & METHODS:Towards this end, ABCG2 polymorphisms and expression were assessed in DNA and tumors from 94 NSCLC patients treated with gefitinib, whereas their associations with toxicity/response and time-to-progression/overall survival were evaluated using Pearson-χ(2) and log-rank-test, respectively. RESULTS:Patients carrying an ABCG2 -15622T/T genotype or harboring at least one TT copy in the ABCG2 (1143C/T, -15622C/T) haplotype developed significantly more grade 2/3 diarrhea (p < 0.01). No associations were found between polymorphisms and outcome. Consistently, ABCG2 protein levels in tumors were not significantly different between patients harboring different ABCG2 variants. CONCLUSION:The ABCG2 -15622C/T polymorphism and ABCG2 (1143C/T, -15622C/T) haplotype resulted in a gefitinib-dependent, moderate-to-severe diarrhea suggesting that these pharmacogenetic markers should be considered to optimize NSCLC treatment.
journal_name
Pharmacogenomicsjournal_title
Pharmacogenomicsauthors
Lemos C,Giovannetti E,Zucali PA,Assaraf YG,Scheffer GL,van der Straaten T,D'Incecco A,Falcone A,Guchelaar HJ,Danesi R,Santoro A,Giaccone G,Tibaldi C,Peters GJdoi
10.2217/pgs.10.172subject
Has Abstractpub_date
2011-02-01 00:00:00pages
159-70issue
2eissn
1462-2416issn
1744-8042journal_volume
12pub_type
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