胡芳,付江萍,吴海波,方向东
HU Fang,FU Jiangping,WU Haibo,FANG Xiangdong

• 1:达州市中心医院

摘要(Abstract)：

目的:探讨乳腺癌患者CYP2D6基因多态性与内分泌治疗药物三苯氧胺(TAM)疗效的相关性。方法:行TAM内分泌治疗的153例乳腺癌患者,采用PCR法检测其CYP2D6基因多态性位点基因型,分析患者基因型与临床病理参数、血清TAM及4-OH-TAM浓度、不良反应、3年及5年无病生存率、肿瘤复发及患者死亡率的相关性;采用Logistic多元回归分析乳腺癌患者TAM内分泌治疗临床效果的影响因素。结果:153例乳腺癌患者中基因型为Wt/Wt、Wt/*10、*10/*10,分别有69例、61例、23例,占45.10%、39.87%、15.03%;Wt/Wt、Wt/*10、*10/*10三种基因型乳腺癌患者年龄、肿瘤直径、组织类型、TNM分期以及腋窝淋巴结转移的差异均无统计学意义(P>0.05),Wt/Wt及Wt/*10基因型患者TAM、4-OH-TAM血清浓度明显高于*10/*10基因型患者,差异具有统计学意义(P<0.05);CYP2D6基因Wt/Wt基因型乳腺癌患者中无不良反应者所占比例明显低于Wt/*10、*10/*10基因型患者(P<0.05),Wt/Wt及Wt/*10基因型乳腺癌患者复发率及死亡率明显低于*10/*10基因型患者(P<0.05),3年、5年无病生存患者比例高于*10/*10基因型患者比例(P<0.05);Logistic回归分析结果显示,乳腺癌患者采用TAM进行内分泌治疗的效果与年龄、肿瘤大小、腋窝淋巴结转移、CYP2D6基因型及TNM分期相关(P<0.05)。结论:CYP2D6基因*10/*10基因型患者接受TAM治疗后体内血药浓度较低、复发率及死亡率较高,该基因型可作为预测乳腺癌患者行三苯氧胺治疗预后的独立危险因素。
Objective: To investigate the correlation between CYP2 D6 gene polymorphism and endocrine therapy with tamoxifen( TAM) on breast cancer patients. Methods: 153 cases of breast cancer patients who were treated with TAM endocrine therapy were selected as the research object,and the CYP2 D6 gene polymorphism were detected by PCR. To research the correlation between genotype and clinical pathological parameters,serum TAM,4-OH-TAM concentration,adverse reaction,3 years and 5 years disease-free survival rate,carcinoma recurrence rate and mortality rate of patients; multivariate Logistic regression analysis was adopted to analyze the influencing factors of endocrine therapy clinical efficacy in patients with breast cancer. Results: The genotype ratios of Wt/Wt,Wt/* 10 and* 10/* 10 of objects were 45. 10%( 69),39. 87%( 61) and 15. 03%( 23) respectively. There were no significant differences in the clinicopathological parameters of the three genotypes of Wt/Wt,Wt/* 10 and * 10/* 10 in terms of age,carcinoma diameter,lesion type,TNM staging and axillary lymph node metastasis( P > 0. 05). The serum concentrations of TAM and 4-OH-TAM in patients with Wt/Wt and Wt/* 10 genotypes were obviously higher than those of * 10/* 10 genotype( P < 0. 05).The proportion of no adverse reaction in Wt/Wt genotype was obviously lower than that of Wt/* 10 and* 10/* 10 genotype( P < 0. 05). The recurrence rate and mortality rate of Wt/Wt and Wt/* 10 genotype patients were obviously lower than that of * 10/* 10 genotype( P < 0. 05). There was no significant correlation between Wt/Wt and Wt/* 10 genotype in 3 and 5 years' disease-free survival rate( P> 0. 05). Multivariate Logistic regression analysis showed that the effect of endocrine therapy by TAM in breast cancer patients was significantly related to age,tumor size,axillary lymph node metastasis,CYP2 D6 genotype and TNM stage( P < 0. 05). Conclusion: CYP2 D6 gene * 10/* 10 genotype patients after TAM treatment illustrated low blood concentration,high recurrence rate and mortality rate,the genotype could be used as independent predictors of breast cancer patients with tamoxifen treatment and prognosis.

关键词(KeyWords)： 乳腺肿瘤;癌;三苯氧胺;细胞色素P450;基因;多态性,单核苷酸
breast neoplasm;carcinoma;tamoxifen;cytochrome P450;gene;polymorphism,single nucleotide

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 胡芳,付江萍,吴海波,方向东
HU Fang,FU Jiangping,WU Haibo,FANG Xiangdong

DOI: 10.19367/j.cnki.1000-2707.2018.08.016

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