乳腺癌患者CYP2C19和UGT1A1基因多态性与他莫昔芬治疗效果的关系  

Relationship between CYP2C19,UGT1A1 gene polymorphisms and tamoxifen therapy in breast cancer patients

作　　者：彭娟[1] 王潇 张延芳[1] Peng Juan;Wang Xiao;Zhang Yanfang(Department of Clinical Laboratory,Jinan Fourth People’s Hospital,Jinan 250031,China)

机构地区：[1]济南市第四人民医院检验科,济南250031

出　　处：《中华内分泌外科杂志（中英文）》2024年第5期652-655,共4页Chinese Journal of Endocrine Surgery

基　　金：2023年度山东省卫生健康委员会科研项目(SH20230055)。

摘　　要：目的探讨乳腺癌患者CYP2C19和UGT1A1基因多态性与他莫昔芬治疗效果的关系。方法选择济南市第四人民医院2021年2月至2023年3月诊治的100例乳腺癌患者,术后均给予他莫昔芬治疗。采用实时聚合酶链式反应(polymerase chain reaction,PCR)法检测CYP2C19和UGT1A1基因多态性,并分析患者CYP2C19和UGT1A1基因多态性与他莫昔芬治疗效果的关系。结果100例乳腺癌患者中,CYP2C19野生型(G/G)和突变型(G/A、A/A)分布频率分别为49.00%、51%;UGT1A1*28野生型和突变型分布频率分别为74.00%、26.00%;UGT1A1*6野生型和突变型分布频率分别为69.00%、31.00%;CYP2C19、UGT1A1*28和UGT1A1*6的野生型和突变型患者在发病年龄、月经状态、病理类型、临床分期、雌激素受体(estrogen receptor,ER)阳性、孕激素受体(progesterone receptor,PR)阳性、激素受体(hormone receptor,HR)阳性上比较,差异统计学意义(CYP2C19的χ^(2)值分别为1.43、0.38、5.52、0.61、1.39、0.01、0.26、1.16,UGT1A1*28的χ^(2)值分别为0.63、0.00、2.88、0.08、1.94、0.61、2.74、0.30,UGT1A1*6的χ^(2)值分别为0.90、0.10、0.75、0.09、1.18、0.11、0.00、0.37,P>0.05)。CYP2C19、UGT1A1*28和UGT1A1*6野生型患者治疗有效率均高于突变型(χ^(2)值分别为4.67、4.86、5.93,P<0.05);Logistic回归分析结果显示CYP2C19、UGT1A1*28和UGT1A1*6的基因型均为影响他莫昔芬治疗效果的独立危险因素(β值分别为0.465、0.557、0.568,P<0.05)。结论乳腺癌患者CYP2C19和UGT1A1基因多态性与他莫昔芬治疗效果密切相关,且还会导致患者不良反应增加。临床上有必要对采用他莫昔芬治疗的乳腺癌患者进行CYP2C19和UGT1A1基因多态性检测,以进一步优化个体化药物治疗。ObjectiveTo investigate the relationship between CYP2C19,UGT1A1 gene polymorphisms and tamoxifen therapy in breast cancer patients.MethodsA total of 100 breast cancer patients diagnosed and treated in our hospital from Feb.2021 to Mar.2023 were chosen and given tamoxifen treatment after surgery.Polymerase chain reaction(PCR)was used to detect CYP2C19 and UGT1A1 gene polymorphisms,and the relationship between CYP2C19,UGT1A1 gene polymorphisms and tamoxifen treatment effect was analyzed.ResultsIn 100 patients with breast cancer,the distribution frequencies of CYP2C19 wild type(G/G)and mutant type(G/A,A/A)were 49.00%and 51%,respectively;The distribution frequencies of wild type and mutant UGT1A1*28 were 74.00%and 26.00%,respectively;The distribution frequencies of wild type and mutant UGT1A1*6 were 69.00%and 31%,respectively;There was no statistically significant difference between CYP2C19,UGT1A1*28 and UGT1A1*6 wild type and mutant patients in the age of onset,menstrual status,pathological type,clinical stage,estrogen receptor(ER)positive,progesterone receptor(PR)positive,hormone receptor(HR)positive(χ^(2) values of CYP2C19 were 1.43,0.38,5.52,0.61,1.39,0.01,0.26,1.16,χ^(2) values of UGT1A1*28 were 0.63,0.00,2.88,0.08,1.94,0.61,2.74,0.30,theχ^(2) values of UGT1A1*6 were 0.90,0.10,0.75,0.09,1.18,0.11,0.00,0.37,P>0.05);The therapeutic effectiveness of CYP2C19,UGT1A1*28 and UGT1A1*6 wild type patients was higher than that of mutant type(χ^(2)=4.67,4.86,5.93,P<0.05);Logistic regression analysis showed that CYP2C19,UGT1A1*28 and UGT1A1*6 genotypes were independent risk factors for tamoxifen treatment effect(β=0.465,0.557,0.568,P<0.05).ConclusionsCYP2C19 and UGT1A1 gene polymorphisms are closely associated with tamoxifen treatment in breast cancer patients,and also lead to increased adverse reactions in patients.It is necessary to conduct CYP2C19 and UGT1A1 gene polymorphisms when tamoxifen is used in breast cancer patients to further optimize individualized drug therapy.

关 键 词：乳腺癌 CYP2C19 UGT1A1 基因多态性 他莫昔芬 

分 类 号：R737.9[医药卫生—肿瘤]