Single nucleotide polymorphisms of ABCC5 and ABCG1 transporter genes correlate to irinotecan-associated gastrointestinal toxicity in colorectal cancer patients: a DMET microarray profiling study (Articolo in rivista)

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  • Single nucleotide polymorphisms of ABCC5 and ABCG1 transporter genes correlate to irinotecan-associated gastrointestinal toxicity in colorectal cancer patients: a DMET microarray profiling study (Articolo in rivista) (literal)
Anno
  • 2011-01-01T00:00:00+01:00 (literal)
Alternative label
  • Maria Teresa Di Martino, Mariamena Arbitrio, Emanuela Leone, Pietro Hiram Guzzi, Maria Saveria Rotundo, Domenico Ciliberto, Vera Tomaino, Fernanda Fabiani, Danilo Talarico, Pasquale Sperlongano, Patrizia Doldo, Mario Cannataro, * Michele Caraglia, Pierfrancesco Tassone, * Pierosandro Tagliaferri (2011)
    Single nucleotide polymorphisms of ABCC5 and ABCG1 transporter genes correlate to irinotecan-associated gastrointestinal toxicity in colorectal cancer patients: a DMET microarray profiling study
    in Cancer biology & therapy (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Maria Teresa Di Martino, Mariamena Arbitrio, Emanuela Leone, Pietro Hiram Guzzi, Maria Saveria Rotundo, Domenico Ciliberto, Vera Tomaino, Fernanda Fabiani, Danilo Talarico, Pasquale Sperlongano, Patrizia Doldo, Mario Cannataro, * Michele Caraglia, Pierfrancesco Tassone, * Pierosandro Tagliaferri (literal)
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  • 7 (literal)
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  • Maria Teresa Di MartinoMagna Graecia University and Tommaso Campanella Cancer Center; Catanzaro, ItalyMariamena ArbitrioInstitute of Neurological Science-National Council of Research-UOS of Pharmacology; Catanzaro, ItalyEmanuela LeoneMagna Graecia University and Tommaso Campanella Cancer Center; Catanzaro, ItalyPietro Hiram GuzziMagna Graecia University, Catanzaro, ItalyMaria Saveria RotundoMagna Graecia University and Tommaso Campanella Cancer Center; Catanzaro, ItalyDomenico CilibertoMagna Graecia University and Tommaso Campanella Cancer Center; Catanzaro, ItalyVera TomainoMagna Graecia University, Catanzaro, ItalyFernanda FabianiSecond University of Naples; Naples, Magna Graecia University and Tommaso Campanella Cancer Center; Catanzaro, ItalyDanilo TalaricoMagna Graecia University and Tommaso Campanella Cancer Center; Catanzaro, ItalyPasquale SperlonganoSecond University of Naples; Naples, ItalyPatrizia DoldoMagna Graecia University and Tommaso Campanella Cancer Center; Catanzaro, ItalyMario CannataroMagna Graecia University, Catanzaro, ItalyMichele Caraglia*Corresponding author: michele.caraglia@unina2.itSecond University of Naples; Naples, ItalyPierfrancesco TassoneMagna Graecia University and Tommaso Campanella Cancer Center; Catanzaro, Italy; Temple University's College of Science & Technology; Philadelphia, PA USAPierosandro Tagliaferri*Corresponding author: tagliaferri@unicz.itMagna Graecia University and Tommaso Campanella Cancer Center; Catanzaro, Italy (literal)
Titolo
  • Single nucleotide polymorphisms of ABCC5 and ABCG1 transporter genes correlate to irinotecan-associated gastrointestinal toxicity in colorectal cancer patients: a DMET microarray profiling study (literal)
Abstract
  • Recent findings have disclosed the role of UDP-glucuronosyltransferase (UGT) 1A1*28 on the haematological toxicity induced by irinotecan (CPT-11), a drug commonly used in the treatment of metastatic colorectal cancer (mCRC). We investigated the pharmacogenomic profile of irinotecan-induced gastrointestinal (GI) toxicity by the novel drug-metabolizing enzyme and transporter (DMET) microarray genotyping platform. Twenty-six mCRC patients who had undergone to irinotecan-based chemotherapy were enrolled in a case (patients experiencing >= grade 3 gastrointestinal, (GI) toxicity) - control (matched patients without GI toxicity) study. A statistically significant difference of SNP genotype distribution was found in the case versus control group. The homozygous genotype C/C in the (rs562) ABCC5 gene occurred in 6/9 patients with GI toxicity versus 1/17 patients without GI toxicity (P=0.0022). The homozygous genotype G/G in the (rs425215) ABCG1 was found in 7/9 patients with GI toxicity versus 4/17 patients without GI toxicity (P=0.0135). The heterozygous genotype G/A in the 388G>A (rs2306283) OATP1B1/SLCO1B1 was found in 3/9 patients with grade >= 3 GI toxicity vs. 14/17 patients without GI toxicity (P=0.0277). DNA extracted from peripheral blood cells was genotyped by DMET Plus chip on Affymetrix array system. Genotype association was calculated by Fisher's exact test (two tailed) and relevant SNPs were further analyzed by direct sequencing. We have identified 3 SNPs mapping in ABCG1, ABCC5 and OATP1B1/SLCO1B1 transporter genes associated with GI toxicity induced by irinotecan in mCRC patients expanding the available knowledge of irinogenomics. The DMET microarray platform is an emerging technology for easy identification of new genetic variants for personalized medicine. (literal)
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