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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 relationship between the CYP19 polymorphism and the efficacy and adverse reactions of aromatase inhibitors (AIs). Methods: The oral mucosa of 78 patients with relapsed and metastasized breast cancer who took AIs were scored. The polymorphisms of rs4646 and rs10046 in CYP19 gene were detected by Real-time RT-PCR, and their clinical pathological characteristics, prognosis and adverse reactions Relationship. Results: The positive rates of CYP19 rs4646 and rs10046 mutations in 44 cases of metastatic breast cancer were 44.9% (35/78) and 52.6% (41/78), respectively. CYP19 gene polymorphism and clinicopathological factors (P> 0.05). The Kaplan-Meier survival analysis showed that the mean DFS of the mutation group of rs4646 and rs10046 in CYP19 was longer than that in the wild group (χ ~ 2 = 24.96, P <0.001; χ ~ 2 = 14.00, P <0.001) . Cox regression analysis showed that both the tumor grade (grade Ⅲ vs grade Ⅰ, HR = 2.73, 95% CI: 1.48-5.06, P = 0.01) and rs10046 (HR = 2.54, 95% CI: 1.02-6.31, P = 0.04) Is to extend the life-saving disease-free unfavorable factors. The rs4646 mutation (HR = 0.13, 95% CI: 0.05-0.35, P = 0.01) was a favorable factor for prolonging disease-free survival. The incidences of fever flushing and bone pain in CYP19 rs4646 mutant patients were 22.9% and 37.1%, respectively, significantly higher than those in wild type patients (11.6% vs.18.6%, P = 0.03). Conclusion: The SNPs of rs4646 and rs10046 in CYP19 are related to the efficacy and side effects of AIs in breast cancer. Before the administration of AIs, CTP19 rs4646 and rs10046 genotypes should be recommended.