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Synergistic interaction of ABCB1 and ABCG2 polymorphisms predicts the prevalence of toxic encephalopathy during anticancer chemotherapy

The Pharmacogenomics Journal volume 8, pages 321–327 (2008)Cite this article

Abstract

Polymorphisms of the ABCB1 (MDR1) and ABCG2 (BCRP) genes were reported to alter the expression and function of these drug transporters. Both proteins are present at the main pharmacokinetic barriers including the blood–brain barrier. Data from 291 children with acute lymphoblastic leukaemia were analysed in this retrospective study. ABCB1 3435T>C, 2677G>T/A, 1236C>T and ABCG2 421C>A, 34G>A genotypes were determined. Encephalopathy episodes were more frequent among those with ABCB1 3435TT genotype than in the 3435CC/CT group (odds ratio (OR) 3.5; P=0.03). Patients with the ABCG2 421A allele tended to have more complications than wild type homozygotes (OR=2.0; P=0.25). The rate of the adverse effect was similar in those harbouring no or only one of the predisposing genotypes, that is, either ABCB1 3435TT or ABCG2 421AA/AC. However, significantly more children suffered encephalopathy in the group with both predisposing genotypes (OR=12.3; P=0.005). In conclusion, these variations exert synergistic effect in predisposing patients to toxic neurological complications of chemotherapy.

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Acknowledgements

We are grateful to all the nurses, doctors and patients who took part in the study. We thank Dσra Lippai, Xιnia Majorosi, Melinda Rácz, Veronika Galasz, Erika Tσth, Gábor Váradi, Krisztina Tσth and Judit Bali for technical assistance. This study was financially supported by grants from the Hungarian Scientific Research Fund (T042500) and the Economic Competitiveness Operational Programme, Hungary (GVOP 3.1.1-2004-05-0022/3.0).

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Authors and Affiliations

  1. Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary

    D J Erdιlyi, Á Fιlnι-Semsei & A Falus

  2. 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary

    D J Erdιlyi, G Fekete & G T Kovács

  3. Laborigo Molecular Diagnostics Ltd., Budapest, Hungary

    E Kámory, B Csókay & A Zalka

  4. Department of Molecular Diagnostics, National Medical Center, Budapest, Hungary

    H Andrikovics & A Tordai

  5. Department of Paediatrics, University of Debrecen, Debrecen, Hungary

    C Kiss

  6. Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden

    I Janszky

  7. Immunogenomics Research Group, Hungarian Academy of Sciences, Budapest, Hungary

    C Szalai

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  1. D J Erdιlyi
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Correspondence to D J Erdιlyi.

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Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj)

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Erdιlyi, D., Kámory, E., Csókay, B. et al. Synergistic interaction of ABCB1 and ABCG2 polymorphisms predicts the prevalence of toxic encephalopathy during anticancer chemotherapy. Pharmacogenomics J 8, 321–327 (2008). https://doi.org/10.1038/sj.tpj.6500480

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