UGT2B7-161基因多态性预测接受EC-TH方案辅助化疗HER-2阳性乳腺癌患者心脏毒性风险的价值

UGT2B7-161 single nucleotide polymorphism in predicting the occurrence of cardiotoxicity in HER-2 positive breast cancer patients underwent EC-TH adjuvant chemotherapy

目的探讨尿苷二磷酸葡萄糖醛酸转移酶2B7(UGT2B7)-161基因多态性预测接受表柔比星+环磷酰胺序贯多西他赛和曲妥珠单抗(EC-TH)方案辅助化疗的人类表皮生长因子受体2(HER-2)阳性乳腺癌患者心脏毒性风险的价值。方法收集2014年1月至2016年12月76例接受术后EC-TH方案辅助化疗的HER-2阳性乳腺癌患者,采集血液样本后采用实时荧光定量PCR检测UGT2B7-161基因的多态性。在接受化疗前(M0)、化疗开始后第3个月(M3)、第6个月(M6)、第9个月(M9)、第12个月(M12)和第15个月(M15)时进行心脏毒性评估,评估指标包括左心室射血分数,发生心力衰竭、急性冠状动脉综合征或重度威胁生命的心律失常的发生情况。结果 76例接受术后EC-TH方案辅助化疗的HER-2阳性乳腺癌患者心脏毒性事件发生总数为63例次,无1例出现心力衰竭、急性冠状动脉综合征以及重度威胁生命的心律失常。UGT2B7-161基因CC、CT、TT表型的患者例数分别为36例(47.3%)、31例(40.8%)和9例(11.8%)。不同基因表型患者的年龄、体质量指数(BMI)、吸烟史、伴随性疾病、ECOG评分以及心脏功能均无显著差异(P>0.05)。全组20例(26.3%)患者发生心脏毒性事件, UGT2B7-161 TT和CT基因型患者发生心脏毒性事件的比例(n=5,12.5%)低于CC基因型(n=15,41.7%)患者(P=0.004)。Logistic多因素回归分析显示,UGT2B7-161基因表型、BMI和心肌肌钙蛋白I均为影响心脏毒性发生风险的独立因素。结论 UGT2B7-161基因多态性可作为接受EC-TH方案辅助化疗HER-2阳性乳腺癌患者心脏毒性发生风险的潜在预测因子。

Objective To explore the value of uridine diphosphate-glucuronosyltransferase 2B7(UGT2B7)-161 single nucleotide polymorphism in predicting the occurrence of cardiotoxicity in Chinese human epidermal growth factor 2(HER-2)positive breast cancer patients underwent epirubicin+cyclophosphamide-taxotere-trastuzumab(EC-TH)adjuvant chemotherapy.Methods From January 2014 to December 2016,a total of 76 HER-2 positive breast cancer patients receiving EC-TH adjuvant chemotherapy were enrolled in this study and blood samples were collected.Polymerase chain reaction(PCR)was conducted for determining UGT2B7-161 genotypes.Cardiotoxicity was assessed at baseline(M 0),month(M)3,M 6,M 9,M 12 and M 15 of adjuvant treatment.The following assessments,including left ventricle ejection fraction(LVEF)was conducted,and the incidence of heart failure,acute coronary artery syndrome or fatal arrhythmia was recorded.Results There were 63 cardiotoxicity events among 76 patients with HER-2 positive breast cancer.Heart failure,acute coronary artery syndrome or fatal arrhythmia were not observed at M 0,M 3,M 6,M 9,M 12 and M 15 of EC-TH regimen adjuvant treatment.There were 36(47.3%),31(40.8%)and 9(11.8%)patients carrying UGT2B7-161 CC,CT and TT genotypes respectively.There was no association between UGT2B7-161 single nucleotide polymorphism and characteristic features(age,body mass index,smoking history,complications,ECOG scores and heart function)at baseline.There were 20 patients(26.3%)were found cardiotoxicity in 76 cases of HER-2 positive breast cancer receiving EC-TH adjuvant chemotherapy.The occurrence of cardiotoxicity was decreased in UGT2B7-161 TT and CT genotypes(12.5%)compared with CC genotype(41.7%)with statistical significance(P=0.004).Multivariate logistic regression model analysis exhibited that UGT2B7-161 genotypes,BMI and N terminal pro B type natriuretic peptide were independent factors influencing the risk of cardiotoxicity.Conclusion UGT2B7-161 single nucleotide polymorphism is a potential predictive factor for cardiotoxicity in HER-2 positive breast cancer patients receiving EC-TH adjuvant chemotherapy.