A Uridine Glucuronosyltransferase 2B7 Polymorphism Predicts Epirubicin Clearance and Outcomes in Early-Stage Breast Cancer

Michael B. Sawyer, Edith Pituskin, Sambasivarao Damaraju, Robert Bies, Larissa J. Vos, Carla M M Prado, Michelle Kuzma, Andrew G. Scarfe, Mark Clemons, Katia Tonkin, Heather Jane Au, Sheryl Koski, Anil A. Joy, Michael Smylie, Karen King, Diana Carandang, Vijaya L. Damaraju, John Hanson, Carol E. Cass, John R. Mackey

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7), an enzyme rich in single nucleotide polymorphisms (SNPs). We studied whether the -161 C > T germline SNP in UGT2B7 was related to epirubicin metabolism and whether differences exist in the toxicity and efficacy of epirubicin-based chemotherapy among patients who were TT homozygotes, CT heterozygotes, and CC homozygotes. Patients and Methods A total of 132 women with non-metastatic breast cancer receiving FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) were prospectively enrolled. Toxicity was assessed in cycle 1 using the National Cancer Institute Common Toxicity Criteria, version 2.0. Results The sequence at -161 was studied in 132 subjects; 37 were TT homozygotes, 63 were CT heterozygotes, 26 were CC homozygotes, and 6 could not be genotyped. The CC genotype patients had decreased epirubicin clearance (median, 103.3 L/hr) compared with the CT/TT genotype patients (median, 134.0 L/hr; P =.002). The CC homozygous patients had an increased risk of grade 3 to 4 leukopenia compared with the TT homozygotes or heterozygotes (P =.038 and P =.032, respectively). TT homozygotes or heterozygotes had an increased risk of early recurrence (P =.039; χ2 test). Conclusion The results of the present prospective pharmacogenetic study suggest that the UGT2B7 -161 C > T SNP correlate with drug metabolism, toxicity, and efficacy in patients receiving epirubicin chemotherapy. Further studies of this UGT2B7 SNP as a predictor of epirubicin toxicity and efficacy are warranted.

Original languageEnglish (US)
Pages (from-to)139-144e3
JournalClinical Breast Cancer
Volume16
Issue number2
DOIs
StatePublished - Apr 1 2016

Keywords

  • Drug clearance
  • Single nucleotide polymorphisms
  • SNP
  • Toxicity
  • UGT2B7

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Sawyer, M. B., Pituskin, E., Damaraju, S., Bies, R., Vos, L. J., Prado, C. M. M., Kuzma, M., Scarfe, A. G., Clemons, M., Tonkin, K., Au, H. J., Koski, S., Joy, A. A., Smylie, M., King, K., Carandang, D., Damaraju, V. L., Hanson, J., Cass, C. E., & Mackey, J. R. (2016). A Uridine Glucuronosyltransferase 2B7 Polymorphism Predicts Epirubicin Clearance and Outcomes in Early-Stage Breast Cancer. Clinical Breast Cancer, 16(2), 139-144e3. https://doi.org/10.1016/j.clbc.2015.09.006