S4646 polymorphism in CYP19A1 gene is associated with the efficacy of hormone therapy in early breast cancer.
S4646 polymorphism in CYP19A1 gene is associated with the efficacy of hormone therapy in early breast cancer.
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发表时间：
2015-05
影响因子：
1.4
通讯作者：
X. Shao;Jinwei Cai;Yabing Zheng;Ji-wen Wang;Jianguo Feng;Yuan Huang;Lei Shi;Zhanhong Chen;Yong Guo;Xiaojia Wang
中科院分区：
文献类型：
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作者：
X. Shao;Jinwei Cai;Yabing Zheng;Ji-wen Wang;Jianguo Feng;Yuan Huang;Lei Shi;Zhanhong Chen;Yong Guo;Xiaojia Wang
目的验证在激素受体(HR)阳性的早期乳腺癌中，CYP19A1基因多态性与激素治疗的临床结果之间的潜在关联。方法对287例HR阳性的早期乳腺癌患者进行CYP19A1 rs4646(C/A)基因分型。评估CYP19A1 rs4646基因与无病生存期(DFS)的相关性。结果携带少量等位基因(AA或AC)的女性比携带纯合子常见等位基因(CC)的女性有更好的DFS(AA或AC vs.CC：62.7月vs.55.6月；危险比(HR)，0.745；95%CI，0.562~0.988；P=0.04)。多因素分析进一步证实了这种差异(HR，0.681；95%CI，0.506-0.917；P=0.011)。在绝经前妇女中，AA基因型与延长的DFS相关(AA和CC或AC分别为98.2个月和56.2月；HR，0.425；95%CI，0.198-0.914；P=0.024)。此外，与携带纯合子C等位基因的妇女相比，携带A等位基因的妇女有更好的DFS(AA或AC vs.CC：62.7月vs.55.6月；HR，0.709；95%CI，0.516-0.975；P=0.033)。COX回归模型进一步证实了上述结果(HR，0.336，0.670；95%CI，0.160-0.836，0.479-0.938；P=0.017，0.019)。在绝经后妇女中，rs4646基因与DFS显著相关(AA、AC、CC分别为32.7月、56.3月；P=0.011)。携带AA变异的妇女的无病生存期(32.7月vs70.6月；HR，3.613；95%CI，1.380~9.457；P=0.005)。经多因素分析调整后，AA基因仍是DFS的独立预后因素(HR，3.614；95%CI，1.308~9.991；P=0.013)。结论CYP19A1 rs4646纯合次要等位基因(AA)与激素治疗改善绝经前HR阳性早期乳腺癌患者的临床疗效显著相关，但对绝经后妇女的影响较差。这些发现是新的，如果得到证实，CYP19A1 rs4646基因多态可能为更好地选择内分泌治疗提供预测性信息。
PURPOSE The aim was to verify the potential association between CYP19A1 genetic polymorphisms and clinical outcome of hormone therapy in hormone receptor (HR)-positive early breast cancer. METHODS Genotyping for CYP19A1 rs4646 (C/A) polymorphism was performed on 287 women with HR-positive early breast cancer. Associations were evaluated between CYP19A1 rs4646 genotypes and disease-free survival (DFS). RESULTS Totally, women with the minor allele (AA or AC) had an improved DFS when compared with those carrying the homozygous common allele (CC) (AA or AC vs. CC: 62.7 months versus 55.6 months; Hazard ratio (HR), 0.745; 95% CI, 0.562-0.988; P=0.04). The difference was further demonstrated by multivariate analyses (HR, 0.681; 95% CI, 0.506-0.917; P=0.011). In premenopausal women, AA genotype was associated with a prolonged DFS (AA versus CC or AC: 98.2 months versus 56.2 months; HR, 0.425; 95% CI, 0.198-0.914; P=0.024). In addition, women with the A allele had an improved DFS when compared with those carrying the homozygous C allele (AA or AC vs. CC: 62.7 months versus 55.6 months; HR, 0.709; 95% CI, 0.516-0.975; P=0.033). These findings were further confirmed by the Cox regression model (HR, 0.336, 0.670; 95% CI, 0.160-0.836, 0.479-0.938; P=0.017, 0.019). In postmenopausal women, rs4646 genotypes were significantly associated with DFS (AA versus AC versus CC: 32.7 months versus not reached versus 56.3 months; P=0.011). Women carrying AA variant had a poorer DFS than those with CC or AC genotypes (32.7 months versus 70.6 months; HR, 3.613; 95% CI, 1.380-9.457; P=0.005). Furthermore, being adjusted by the patients features in multivariate analyses, AA genotype remained an independent prognostic factor for DFS (HR, 3.614; 95% CI, 1.308-9.991; P=0.013). CONCLUSIONS The homozygous minor allele (AA) of CYP19A1 rs4646 is significantly associated with improved clinical outcome of hormone therapy in premenopausal HR-positive early breast cancer patients, but with a worse impact on postmenopausal women. The findings are novel, if confirmed, genotyping for CYP19A1 rs4646 polymorphism may provide predictive information for better selection of endocrine treatment.