Functional Variant rs4442975 Modulating FOXA1 Binding Affinity Can Influence Bone Marrow Suppression during Neoadjuvant Chemotherapy for Luminal A Type Breast Cancer
Functional Variant rs4442975 Modulating FOXA1 Binding Affinity Can Influence Bone Marrow Suppression during Neoadjuvant Chemotherapy for Luminal A Type Breast Cancer
复制标题
功能变异 rs4442975 调节 FOXA1 结合亲和力可影响 Luminal A 型乳腺癌新辅助化疗期间的骨髓抑制
DOI：
10.1155/2019/7073498
复制
发表时间：
2019-01-01
影响因子：
--
通讯作者：
Zhang, Yi
中科院分区：
文献类型：
--
作者：
Wang, Xin;Feng, Zhongxin;Zhang, Yi
转录因子FOXA 1的表达与雌激素受体（ER）阳性乳腺癌的预后相关，遗传变异rs 4442975可影响FOXA 1的功能。因此，我们在中国人群中研究rs 4442975与管腔A型乳腺癌新辅助化疗疗效的相关性，并评估其毒副作用。175例接受新辅助化疗的管腔A型乳腺癌患者，采用表阿霉素和多西他赛联合方案（ET方案）。以随机方式进行基因分型以鉴定候选遗传变异体。采用非条件Logistic回归分析该变异与新辅助化疗疗效及毒副反应的关系。结果未显示与新辅助化疗疗效的任何正相关性，在相加模型中比值比（OR）为0.73（95%置信区间= 0.27-1.94）。然而，对新辅助化疗毒副作用的分析显示，rs 4442975与骨髓抑制相关，优势模型中OR为0.38（95%置信区间= 0.17-0.73，p = 0.005）。总之，功能性遗传变异rs 4442975与管腔A型乳腺癌新辅助化疗期间的骨髓抑制相关。这些结果可能有助于建立可靠的分子标志物，用于预测管腔A型乳腺癌个性化治疗的预后，从而有助于开发适当的治疗方法。
The expression of the transcription factor FOXA1 is associated with the prognosis of estrogen receptor (ER)-positive breast cancer, and the genetic variant rs4442975 can affect FOXA1 function. Therefore, we investigated the association between rs4442975 and the efficacy of neoadjuvant chemotherapy for luminal A type breast cancer and evaluated its toxic side effects in a Chinese population. One hundred seventy-five patients with luminal A type breast cancer receiving neoadjuvant chemotherapy with a combination protocol of epirubicin and docetaxel (ET protocol) were enrolled in the study. Genotyping was performed in a randomized manner to identify candidate genetic variants. Unconditional logistic regression analysis was used to analyze the association of the variant with the efficacy and side effects of neoadjuvant chemotherapy. The results did not reveal any positive association with the efficacy of neoadjuvant chemotherapy, with an odds ratio (OR) of 0.73 (95% confidence interval = 0.27–1.94) in the additive model. However, analysis of the toxic side effects of neoadjuvant chemotherapy showed that rs4442975 was associated with bone marrow suppression, with an OR of 0.38 (95% confidence interval = 0.17–0.73, p = 0.005) in the dominant model. In summary, the functional genetic variant rs4442975 was associated with bone marrow suppression during neoadjuvant chemotherapy for luminal A type breast cancer. These results may help establish reliable molecular markers for predicting the prognosis of personalized treatment for luminal A type breast cancer and thereby contribute to the development of appropriate therapies.