乳腺癌CYP19基因多态性对芳香化酶抑制剂疗效影响的临床研究  

Clinical Analysis of the Effect of CYP19 Gene Polymorphism on the Clinical Outcomes of Aromatase Inhibitors for Breast Cancer Patients

作　　者：王浩[1] 陶苹[1] 牟鳄贤 田超[1] 李卉[1] 

机构地区：[1]四川省肿瘤医院乳腺科,成都610041

出　　处：《肿瘤预防与治疗》2016年第3期133-138,143,共7页Journal of Cancer Control And Treatment

基　　金：四川省科技厅科技支撑计划(2012FZ0050)

摘　　要：目的：探讨CYP19基因多态性与芳香化酶抑制剂（Aromatase Inhibitors,AIs）疗效及不良反应的相关性。方法：刮取78例服用AIs出现复发转移乳腺癌患者的口腔黏膜,采用Real-time RT-PCR法检测CYP19基因rs4646、rs10046位点多态性,并分析其与临床病理特征,预后及不良反应的关系。结果：78例转移性乳腺癌中检测到CYP19 rs4646、rs10046突变型发生率分别为44.9%（35/78）、52.6%（41/78）。CYP19基因多态性与患者临床病理因素无关（P〉0.05）。Kaplan-Meier生存分析显示,CYP19 rs4646及rs10046位点突变组平均DFS长于野生组,两组间差异有统计学意义（χ~2=24.96,P〈0.001;χ~2=14.00,P〈0.001）。Cox回归分析显示,肿瘤分级（Ⅲ级vsⅠ级,HR=2.73,95%CI：1.48~5.06,P=0.01）和rs10046突变（HR=2.54,95%CI：1.02~6.31,P=0.04）均是延长无病生存时间的不利因素。rs4646突变（HR=0.13,95%CI：0.05~0.35,P=0.01）是延长无病生存的有利因素。CYP19 rs4646突变型患者发热潮红和骨痛的发生率分别为22.9%及37.1%,明显高于野生型患者（11.6%vs.18.6%,P=0.03）。结论：CYP19 rs4646及rs10046位点SNP与乳腺癌AIs的疗效及不良反应相关,服用AIs前均应推荐检测CTP19 rs4646及rs10046基因型。Objective： To investigate the correlation between CYP19 gene polymorphism and the efficacy of aromatase inhibitors（ AIs）,as well as its adverse reactions. Methods： The oral mucosas were scraped from 78 recurrent or metastatic post-menopausal breast cancer patients after the treatment of AIs. Real-time RT-PCR was used to determine CYP19 gene rs4646 and rs10046 polymorphism. The relationship between CYP19 gene polymorphism and the clinicopathological features,including prognosis and adverse reactions of patients was assessed. Results： Of all 78 cases,the incidence of single nucleotide polymorphism（ SNP） in CYP19 rs4646 and rs10046 were 44. 9%（ 35 /78） and 52. 6%（ 41 /78）,respectively. CYP19 gene polymorphism was not related to clinicopathological features of patients（ P〉0. 05）. Survival analysis by Kaplan-Meier showed that the disease-free survival in patients with CYP19 rs4646 and rs10046 mutation was significantly longer than that in patients without CYP19 mutation（ P〈0. 001）. Cox regression analysis showed that tumor classification and rs10046 mutations are unfavorable factors for extending disease-free survival time,however,rs4646 mutation could prolong disease-free survival time. The incidence of fever flush and bone pain in rs4646 mutation cases was22. 9% and 37. 1%,respectively,which was significantly higher than that of the wild type patients. Conclusion： CYP19rs4646 and rs10046 genotype are related to the clinical outcomes of AIs for recurrent or metastatic breast cancer,indicating that the CYP19 genotype should be routinely determined before AIs treatment.

关 键 词：转移性乳腺癌 芳香化酶抑制剂 单核苷酸多态性 CYP19 

分 类 号：R737.9[医药卫生—肿瘤] R730.5[医药卫生—临床医学]