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- Title
Impact of functional ABCG2 polymorphisms on the adverse effects of gefitinib in Japanese patients with non-small-cell lung cancer.
- Authors
Akasaka K; Kaburagi T; Yasuda S; Ohmori K; Abe K; Sagara H; Ueda Y; Nagao K; Imura J; Imai Y; Akasaka, Keiichi; Kaburagi, Takayuki; Yasuda, Shin'ichi; Ohmori, Kyoko; Abe, Kaori; Sagara, Hironori; Ueda, Yoshihiko; Nagao, Koshu; Imura, Johji; Imai, Yasuo
- Abstract
<bold>Purpose: </bold>ABCG2 is a half-size ATP-binding cassette transporter implicated in cellular gefitinib transport. Reportedly, the c.421C > A ABCG2 gene polymorphism was associated with gefitinib-induced diarrhea in Caucasian patients with non-small-cell lung cancer. Since c.421C > A ABCG2, resulting in p.Q141K substitution, is more prevalent in Asian populations, the putative relationship between gefitinib-induced adverse effects and this functional polymorphism was investigated in Japanese patients. c.376C > T, resulting in truncated, non-functional ABCG2, was also investigated.<bold>Methods: </bold>ABCG2 gene polymorphisms were evaluated in 75 patients with non-small-cell lung cancer treated with gefitinib 250 mg/day orally, and results were correlated with treatment-related adverse effects.<bold>Results: </bold>Forty (53.3%) patients harbored c.421A ABCG2 on at least one allele, while the remaining 35 (46.7%) were wild type for c.421C > A. No significant group difference was observed in frequency of gefitinib-related diarrhea or other adverse effects. In addition, the only one patient homozygous for the c.421A allele in this study was not affected with gefitinib-induced diarrhea or interstitial lung disease. Two patients (2.7%) were found to harbor the c.376T allele heterozygously. One of the two patients harbored both the c.376T and the c.421A genotypes on distinct alleles. Gefitinib-related interstitial lung disease and severe diarrhea were noted in neither of the two patients.<bold>Conclusions: </bold>In this Japanese population, we did not find an evident association between ABCG2 polymorphisms, c.376C > T and c.421C > A, and susceptibility to gefitinib-induced adverse effects.
- Publication
Cancer Chemotherapy & Pharmacology, 2010, Vol 66, Issue 4, p691
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-009-1211-6