Shao Xiying, Luo Lei, Guo Yong, Xu Xiaohong, Deng Dehou, Feng Jianguo, Ding Yuheng, Mou Hanzhou, Huang Ping, Shi Lei, Huang Yuan, Ye Weiwu, Lou Caijin, Chen Zhanhong, Zheng Yabing, Wang Xiaojia
Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
Zhejiang Institute for Food and Drug Control, Hangzhou, Zhejiang 310052, P.R. China.
Oncol Lett. 2017 Nov;14(5):6156-6162. doi: 10.3892/ol.2017.6984. Epub 2017 Sep 18.
It has been hypothesized that single nucleotide polymorphisms in CYP19A1 gene may alter aromatase activity and circulating steroid hormone levels in females. Therefore, it is biologically reasonable that rs1008805 (A/G) polymorphism may be associated with the clinical outcome of hormone therapy. Genotyping for the rs1008805 polymorphism was performed for 287 females with hormone receptor (HR)-positive early breast cancer, and potential associations were evaluated between rs1008805 genotypes and disease-free survival (DFS). Based on the analysis of the whole cohort, no significant differences were observed between rs1008805 genotypes and DFS. However, in postmenopausal females, rs1008805 variants were significantly associated with DFS (AA vs. AG vs. GG, 89.2 vs. 58.2 vs. 32.7 months; P=0.019). In addition, when the population was divided into two cohorts, females with the GG variant exhibited a significantly poorer DFS [GG vs. AA or AG, 32.7 vs. 70.6 months; hazard ratio (HR), 3.613; 95% confidence interval (CI), 1.380-9.457; P=0.005]. Furthermore, when adjusted for other patient features in multivariate analyses, GG genotype remained an independent prognostic marker for DFS (HR, 3.439; 95% CI, 1.251-9.456; P=0.017). However, there were no significant differences in DFS between patients harboring the minor allele and those with the homozygous common allele (AG or GG vs. AA, 52.4 vs. 89.2 months; HR, 1.288; 95% CI, 0.705-2.353; P=0.408). There were also no associations between rs1008805 polymorphism and DFS for premenopausal females. In conclusion, the homozygous minor allele (GG) of rs1008805 was identified to be significantly associated with an inferior clinical outcome of hormone therapy in postmenopausal hormone receptor-positive patients with early breast cancer. If confirmed by further study, genotyping for rs1008805 polymorphism may provide predictive information to improve the selection of endocrine treatment.
据推测，CYP19A1基因中的单核苷酸多态性可能会改变女性体内芳香化酶的活性和循环类固醇激素水平。因此，rs1008805（A/G）多态性可能与激素治疗的临床结果相关，这在生物学上是合理的。对287例激素受体（HR）阳性的早期乳腺癌女性进行了rs1008805多态性的基因分型，并评估了rs1008805基因型与无病生存期（DFS）之间的潜在关联。基于对整个队列的分析，未观察到rs1008805基因型与DFS之间存在显著差异。然而，在绝经后女性中，rs1008805变异与DFS显著相关（AA vs. AG vs. GG，分别为89.2个月、58.2个月和32.7个月；P=0.019）。此外，当将人群分为两个队列时，携带GG变异的女性DFS显著较差[GG vs. AA或AG，分别为32.7个月和70.6个月；风险比（HR）为3.613；95%置信区间（CI）为1.380 - 9.457；P=0.005]。此外，在多变量分析中对其他患者特征进行调整后，GG基因型仍然是DFS的独立预后标志物（HR为3.439；95%CI为1.251 - 9.456；P=0.017）。然而，携带次要等位基因的患者与纯合常见等位基因（AG或GG vs. AA）的患者在DFS方面没有显著差异（分别为52.4个月和89.2个月；HR为1.288；95%CI为0.705 - 2.353；P=0.408）。绝经前女性的rs1008805多态性与DFS之间也没有关联。总之，rs1008805的纯合次要等位基因（GG）被确定与绝经后激素受体阳性早期乳腺癌患者激素治疗的较差临床结果显著相关。如果进一步研究得到证实，rs1008805多态性的基因分型可能会提供预测信息，以改善内分泌治疗的选择。
