title: Genetic polymorphisms of the adenosine triphosphate-binding cassette transporters (ABCG2, ABCB1) and gefitinib toxicity.
abstract: The purpose of this study is to investigate associations between allelic variations of ABCG2 and ABCB1 with skin toxicity, diarrhea, liver injury and interstitial lung disease (ILD) in gefitinib-treated patients. A prospective clinical study of 83 Japanese patients with non-small-cell lung cancer was performed. Polymorphic loci in ABCG2 and ABCB1 were genotyped, and their effects on gefitinib toxicities were evaluated. ABCG2 34G>A was statistically associated with occurrence of skin rash; 13 (42%) of the 32 patients with at least one variant ABCG2 34G>A allele (G/A and A/A) developed grade 2 or worse skin rash, whereas only 10 (19%) of 51 patients homozygous for the reference allele (G/G) for the wild-type sequence for both alleles did so (P=0.046). There was no significant association between severe toxicities and polymorphisms of ABCG2 421C>A nor ABCB1 3435C>T. The results suggested that ABCG2 34G>A would be useful for predicting grade 2 or worse skin rash.
authors.affiliation: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Tamura
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.forename: Mihoko
authors.initials: M
authors.lastname: Horio
authors.forename: Maki
authors.initials: M
authors.lastname: Ando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Horio
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hasegawa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005076:Exanthema / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011799:Quinazolines / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077156:Gefitinib