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In interaction with gender a common CYP3A4 polymorphism may influence the survival rate of chemotherapy for childhood acute lymphoblastic leukemia

The Pharmacogenomics Journal volume 15, pages 241–247 (2015)Cite this article

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Abstract

CYP3A4 has an important role in the metabolisms of many drugs used in acute lymphoblastic leukemia (ALL) therapy; still, there are practically no publications about the role of CYP3A4 polymorphisms in ALL pharmacogenomics. We genotyped eight common single-nucleotide polymorphisms (SNPs) in the CYP3A4 and CYP3A5 genes in 511 children with ALL and investigated whether they influenced the survival of the patients. We involved additional 127 SNPs in 34 candidate genes and searched for interactions with respect to the survival rates. Significant association between the survival rates and the common rs2246709 SNP in the CYP3A4 gene was observed. The gender of the patients and the rs1076991 in the MTHFD1 gene strongly influenced this effect. We calculated new risk assessments involving the gender-rs2246709 interaction and showed that they significantly outperformed the earlier risk-group assessments at every time point. If this finding is confirmed in other populations, it can have a considerable prognostic significance.

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Acknowledgements

This study was supported by OTKA (Hungarian Scientific Research Fund): K81941 (C Szalai); the Economic Competitiveness Operational Program, Hungary GVOP 3.1.1-2004-05-0022/3.0 (DJ Erdélyi); OTKAPD (Hungarian Scientific Research Fund): 76348 (P Antal) and 109200 ÁF Semsei, János Bolyai Research Scholarship of the Hungarian Academy of Sciences (P Antal) and NKTH (National Research and Technology) TECH_08-A1/2-2008-0120: (C Szalai, P Antal). This work is connected to the scientific program of the ‘Development of quality-oriented and harmonized R+D+I strategy and functional model at BME’ project. This project is supported by the New Széchenyi Plan (Project ID: TÁMOP-4.2.1/B-09/1/KMR-2010-0002).

Web pages for the funding organizations:

OTKA: http://www.otka.hu/

NKTH: www.nih.gov.hu

Bolyai Research Scholarship: http://www.bolyaitestamentum.hu/?m=24

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Authors and Affiliations

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

    A Gézsi, O Lautner-Csorba, Á F Semsei, N Kutszegi & C Szalai

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

    D J Erdélyi, M Hegyi, K Csordás & G Kovács

  3. Department of Measurement and Information Systems, University of Technology and Economics, Budapest, Hungary,

    G Hullám & P Antal

  4. Heim Pal Children Hospital, Budapest, Hungary,

    C Szalai

  5. Csertex Research Laboratory, Budapest, Hungary,

    C Szalai

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  1. A Gézsi
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  2. O Lautner-Csorba
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Correspondence to C Szalai.

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Gézsi, A., Lautner-Csorba, O., Erdélyi, D. et al. In interaction with gender a common CYP3A4 polymorphism may influence the survival rate of chemotherapy for childhood acute lymphoblastic leukemia. Pharmacogenomics J 15, 241–247 (2015). https://doi.org/10.1038/tpj.2014.60

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