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

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• 作者：Michael B. Sawyer¹ ; ² ; ³ ; ^{michael.sawyer@albertahealthservices.ca" class="auth_mail" title="E-mail the corresponding author} ; Edith Pituskin¹ ; Sambasivarao Damaraju⁴ ; Robert R. Bies⁵ ; Larissa J. Vos³ ; Carla. M.M. Prado¹ ; ³ ; Michelle Kuzma¹ ; Andrew G. Scarfe¹ ; ³ ; Mark Clemons⁶ ; Katia Tonkin¹ ; ³ ; Heather-Jane Au¹ ; ³ ; Sheryl Koski¹ ; ³ ; Anil A. Joy¹ ; ³ ; Michael Smylie¹ ; ³ ; Karen King¹ ; ³ ; Diana Carandang⁴ ; Vijaya L. Damaraju² ; ³ ; John Hanson³ ; Carol E. Cass² ; ³ ; John R. Mackey¹ ; ² ; ³
• 关键词：Drug clearance ; UGT2B7 ; Single nucleotide polymorphisms ; SNP ; Toxicity
• 刊名：Clinical Breast Cancer
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：16
• 期：2
• 页码：139-144.e3
• 全文大小：530 K

文摘

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.