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Association of CYP1B1 with hypersensitivity induced by Taxane therapy in breast cancer patients

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Abstract

Taxanes represent a group of anticancer drugs with a wide range of activity against breast cancer. Therapy side effects include haematologic toxicity (neutropenia, leucopenia), peripheral neuropathy and hypersensitivity, and demonstrate inter-individual variations. Since it is known that three genes are implicated in Taxane turnover, namely ABCB1 in the transport, CYP2C8 in the metabolism and CYP1B1 in the activity, we explored the association among polymorphisms (single nucleotide polymorphisms, SNPs) in these three genes and the occurrence of Taxane-induced toxicity. We studied 95 patients affected by breast cancer and under treatment with Taxanes as adjuvant, metastatic or neo-adjuvant therapy. We genotyped them for SNPs in the CYP2C8 (alleles *1, *2, *3 and *4), CYP1B1 (alleles *1 and *3) and ABCB1 (1236 C>T; 2677 G>T/A; 3435 C>T) genes by real-time PCR assay. We observed a significant association between the CYP1B1*3 allele and a lower occurrence of hypersensitivity reactions to Taxane treatment. We speculate that the highest production of 4-hydroxyestradiol (4-OHE2) metabolite by CYP1B1*3 allele could increase the formation of the 4-OHE2-Taxane adduct and possibly inhibit Taxane toxicity. We suggest that CYP1B1 might affect Taxane hypersensitivity therefore representing, if confirmed in a large cohort of patients, an exploratory hypersensitivity predictive biomarker.

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Abbreviations

SNPs:

Single nucleotide polymorphisms

CYP :

Cytochrome P450 superfamily

ABCB1 :

ATP-binding cassette, sub-family B (MDR/TAP), member 1

4-OHE2:

4-Hydroxyestradiol

NCI:

National Cancer Institute

rs:

Reference cluster ID

VAR1:

Homozygous variant 1

HT:

Heterozygous

VAR2:

Homozygous variant 2

NA:

Not applicable

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Acknowledgments

This work was supported by the “Programma Ricerca Regione Università 2007/2009” Area 1A: Innovative Research.: The Contribution of Novel Technologies to the improvement of Diagnosis/Therapies in Breast Cancer by Explorating Susceptibility Genes/Factors (to A. F.).

Conflict of interest statement

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Via Fossato di Mortara, 74, 44121, Ferrara, Italy

    Roberta Rizzo, Olavio R. Baricordi, Paola Rimessi & Alessandra Ferlini

  2. Oncology Unit, St. Anna University Hospital, Corso Giovecca 203, 44121, Ferrara, Italy

    Federica Spaggiari, Monica Indelli & Giorgio Lelli

Authors
  1. Roberta Rizzo
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  2. Federica Spaggiari
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  3. Monica Indelli
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  4. Giorgio Lelli
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  5. Olavio R. Baricordi
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  6. Paola Rimessi
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  7. Alessandra Ferlini
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Corresponding author

Correspondence to Alessandra Ferlini.

Additional information

Roberta Rizzo and Federica Spaggiari contributed equally to this study.

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Rizzo, R., Spaggiari, F., Indelli, M. et al. Association of CYP1B1 with hypersensitivity induced by Taxane therapy in breast cancer patients. Breast Cancer Res Treat 124, 593–598 (2010). https://doi.org/10.1007/s10549-010-1034-5

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  • DOI: https://doi.org/10.1007/s10549-010-1034-5

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