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Impact of functional ABCG2 polymorphisms on the adverse effects of gefitinib in Japanese patients with non–small-cell lung cancer

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

This study was supported in part by research grant from Dokkyo Medical University and Grant-in-Aid for Scientific Research (C) (20590372) from the Ministry of Education, Science, Sports, and Culture of Japan.

Disclosure of potential conflict of interest

The authors declare no potential conflict of interest.

Author information

Authors and Affiliations

  1. Department of Respiratory Medicine, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, Japan

    Keiichi Akasaka, Hironori Sagara & Koshu Nagao

  2. Department of Respiratory Disease, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki, Japan

    Takayuki Kaburagi

  3. Institute for Medical Science, Dokkyo Medical University, Mibu, Tochigi, Japan

    Shin’ichi Yasuda

  4. Joint Research Center, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, Japan

    Kyoko Ohmori

  5. Department of Pathology, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki, Japan

    Kaori Abe

  6. Department of Pathology, Dokkyo Medical University Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama, 343-8555, Japan

    Yoshihiko Ueda & Yasuo Imai

  7. Department of Pathology, Dokkyo Medical University, Mibu, Tochigi, Japan

    Johji Imura

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  1. Keiichi Akasaka
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  2. Takayuki Kaburagi
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  3. Shin’ichi Yasuda
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  5. Kaori Abe
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  6. Hironori Sagara
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  7. Yoshihiko Ueda
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  8. Koshu Nagao
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  9. Johji Imura
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  10. Yasuo Imai
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Correspondence to Yasuo Imai.

Additional information

K. Akasaka and T. Kaburagi contributed equally to this work.

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Akasaka, K., Kaburagi, T., Yasuda, S. et al. Impact of functional ABCG2 polymorphisms on the adverse effects of gefitinib in Japanese patients with non–small-cell lung cancer. Cancer Chemother Pharmacol 66, 691–698 (2010). https://doi.org/10.1007/s00280-009-1211-6

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  • DOI: https://doi.org/10.1007/s00280-009-1211-6

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