Single nucleotide polymorphisms of the aromatase gene (CYP19A1), HER2/neu status, and prognosis in breast cancer patients
Single nucleotide polymorphisms of the aromatase gene (CYP19A1), HER2/neu status, and prognosis in breast cancer patients
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DOI：
10.1007/s10549-007-9822-2
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发表时间：
2008-11-01
影响因子：
3.8
通讯作者：
Strick, Reiner
中科院分区：
文献类型：
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作者：
Fasching, Peter Andreas;Loehberg, Christian R.;Strick, Reiner
目的雌激素暴露与乳腺癌患者的易感性和预后有关。芳香化酶参与雌激素的产生，其表达的改变可能与预后有关。本研究的目的是研究芳香化酶基因CYP19A1的单核苷酸多态性（snp）对乳腺癌患者预后的影响，以及与肿瘤和患者特征的关系。患者和方法本研究分析的队列包括1257例浸润性原发性乳腺癌患者。对rs10046、rs4646和rs700519多态性进行基因分型。结果rs10046和rs4646的变异基因型与her2阳性肿瘤的比例较低相关。rs700519和rs4646与无病生存期（DFS）或总生存期（OS）没有关联。rs10046的变异基因型与更好的5年DFS（风险比0.51;95% CI, 0.32 ~ 0.81; P = 0.004）相关，调整了年龄、淋巴结状态、肿瘤大小分级和激素受体状态。这种效果似乎是在绝经前患者亚组中确定的。结论snp rs10046和rs4646可能影响乳腺癌肿瘤的HER2状态，rs10046基因型与DFS改变相关。芳香化酶多态性的基因型可能影响乳腺癌患者的预后，不仅通过影响雌激素暴露的程度，还通过改变肿瘤特征。
Purpose Estrogen exposure is involved in both breast cancer susceptibility and the prognosis in patients with breast cancer. Aromatase is involved in the production of estrogens, and altered expression of it might be associated with the prognosis. The aim of this study was to examine the effect of single nucleotide polymorphisms (SNPs) in the aromatase gene, CYP19A1, on the prognosis, and in relation to tumor and patient characteristics in a cohort of breast cancer patients. Patients and methods The cohort analyzed in this study consisted of 1,257 patients with invasive primary breast cancer. Polymorphisms rs10046, rs4646 and rs700519 were genotyped within this group. Results The variant genotypes of rs10046 and rs4646 were associated with a lower percentage of HER2-positive tumors. There was no association of rs700519 and rs4646 with disease-free survival (DFS) or overall survival (OS). The variant genotype of rs10046 was significantly associated with a better 5-year DFS (hazards ratio 0.51; 95% CI, 0.32 to 0.81; P = 0.004) adjusted for age, nodal status, tumor size grading, and hormone receptor status. This effect appeared to be determined in the subgroup of premenopausal patients. Conclusion SNPs rs10046 and rs4646 may influence the HER2 status of breast cancer tumors, and rs10046 genotypes are associated with an altered DFS. Genotypes of aromatase polymorphisms may influence the prognosis for breast cancer patients not only by affecting the extent of estrogen exposure but also through an alteration in tumor characteristics.