Yonsei Med J.  2019 Jan;60(1):30-37. 10.3349/ymj.2019.60.1.30.

Correlation of UGT2B7 Polymorphism with Cardiotoxicity in Breast Cancer Patients Undergoing Epirubicin/Cyclophosphamide-Docetaxel Adjuvant Chemotherapy

• Li H
• Hu B
• Guo Z
• Jiang X
• Su X
• Zhang X

• KMID: 2428275
• DOI: http://doi.org/10.3349/ymj.2019.60.1.30

Abstract

PURPOSE
The present study aimed to investigate correlations between uridine glucuronosyltransferase 2B7 (UGT2B7) -161 single nucleotide polymorphism C to T (C>T) and the occurrence of cardiotoxicity in Chinese breast cancer (BC) patients undergoing epirubicin/cyclophosphamide-docetaxel (EC-D) adjuvant chemotherapy.
MATERIALS AND METHODS
427 BC patients who had underwent surgery were consecutively enrolled in this prospective cohort study. All patients were scheduled to receive EC-D adjuvant chemotherapy regimen, and they were divided into UGT2B7 -161 CC (n=141), UGT2B7 -161 CT (n=196), and UGT2B7 -161 TT (n=90) groups according to their genotypes. Polymerase chain reaction was performed for determination of UGT2B7 -161 genotypes. Cardiotoxicity was defined as an absolute decline in left ventricular ejection fraction (LVEF) of at least 10% points from baseline to a value less than 53%, heart failure, acute coronary artery syndrome, or fatal arrhythmia.
RESULTS
LVEF values were lower at cycle (C) 4, C8, 3 months after chemotherapy (M3), M6, M9, and M12 compared to C0 (all p < 0.001), in BC patients undergoing EC-D adjuvant chemotherapy. Cardiotoxicity was recorded for 4.2% of the overall population and was lowest in the UGT2B7 -161 TT group (1.1%), compared to UGT2B7 -161 CT (3.1%) and UGT2B7 -161 CC (7.8%) group (p=0.026). Multivariate logistic regression revealed that UGT2B7 -161 T allele could independently predict a low occurrence of cardiotoxicity in BC patients undergoing EC-D adjuvant chemotherapy (p=0.004).
CONCLUSION
A UGT2B7 -161 T allele serves as a potential biomarker for predicting a low occurrence of cardiotoxicity in BC patients undergoing EC-D adjuvant chemotherapy.

Keyword

UGT2B7; polymorphism; chemotherapy; cardiotoxicity; breast cancer

MeSH Terms

Alleles
Arrhythmias, Cardiac
Asian Continental Ancestry Group
Breast Neoplasms*
Breast*
Cardiotoxicity*
Chemotherapy, Adjuvant*
Cohort Studies
Coronary Vessels
Drug Therapy
Genotype
Glucuronosyltransferase
Heart Failure
Humans
Logistic Models
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Prospective Studies
Stroke Volume
Uridine
Glucuronosyltransferase
Uridine

Figure

• 

  Fig. 1 Study flow. BC, breast cancer; UGT2B7, uridine glucuronosyltransferase 2B7.

• 

  Fig. 2 LVEF during and after adjuvant chemotherapy in BC patients. LVEF values were lower at C4, C8 (M0), M3, M6, M9, and M12, compared to C0 in BC patients undergoing EC-D adjuvant chemotherapy. Comparison between paired time points was performed using Wilcoxon signed-rank sum test. *p<0.001 compared with C0. LVEF, left ventricular ejection fraction; C4/C8, 4th/8th cycle of adjuvant chemotherapy; M3/M6/M9/M12, 3/6/9/12 months after adjuvant chemotherapy; BC, breast cancer.

• 

  Fig. 3 Occurrence of cardiotoxicity after adjuvant chemotherapy in BC patients. (A) The total occurrence of cardiotoxicity was 4.2% in 427 BC patients, and the percentage of cases presenting with heart failure, acute coronary syndrome, life-threatening arrhythmias, and LVEF decreased ≥10% to absolute <53% were 0.5, 0.0, 0.2, and 4.0%, respectively (Two patients presented with both heart failure and LVEF decreased ≥10% to absolute <53%). (B) The occurrence rate of cardiotoxicity in patients with UGT2B7 -161 TT genotype was 1.1%, which was lower than that in patients with UGT2B7 -161 CT (3.1%) and UGT2B7 -161 CC (7.8%) genotypes. Comparison among three groups was conducted using chi-square test, and p<0.05 was considered significant. BC, breast cancer; LVEF, left ventricular ejection fraction; UGT2B7, uridine glucuronosyltransferase 2B7.

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