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Clin Breast Cancer. 2016 Apr;16(2):139-44.e1-3. doi: 10.1016/j.clbc.2015.09.006. Epub 2015 Sep 25.

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

Author information

1
Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Division of Experimental Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, University of Alberta, Edmonton, AB, Canada. Electronic address: michael.sawyer@albertahealthservices.ca.
2
Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada.
3
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
4
Department of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN.
5
Department of Oncology, University of Alberta, Edmonton, AB, Canada.
6
Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, University of Alberta, Edmonton, AB, Canada.
7
Division of Medical Oncology, The Ottawa Hospital Cancer Centre and University of Ottawa, Ottawa, ON, Canada.
8
Division of Experimental Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, University of Alberta, Edmonton, AB, Canada.
9
Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Division of Experimental Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, University of Alberta, Edmonton, AB, Canada.

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/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)) 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; χ(2) 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.

KEYWORDS:

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

PMID:
26452313
DOI:
10.1016/j.clbc.2015.09.006
[Indexed for MEDLINE]

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