A genome-wide association study identifies WT1 variant with better response to 5-fluorouracil, pirarubicin and cyclophosphamide neoadjuvant chemotherapy in breast cancer patients.
A genome-wide association study identifies WT1 variant with better response to 5-fluorouracil, pirarubicin and cyclophosphamide neoadjuvant chemotherapy in breast cancer patients.
复制标题
一项全基因组关联研究发现 WT1 变异对乳腺癌患者的 5-氟尿嘧啶、吡柔比星和环磷酰胺新辅助化疗有更好的反应
DOI：
10.18632/oncotarget.5837
复制
发表时间：
2016-01-26
期刊：
影响因子：
--
通讯作者：
Xie Y
中科院分区：
文献类型：
--
作者：
Wu L;Yao L;Zhang H;Ouyang T;Li J;Wang T;Fan Z;Fan T;Lin B;Yin CC;Xie Y
乳腺癌被认为是遗传和非遗传危险因素相互作用的结果，个体遗传变异可能会影响化疗的疗效。在这里，我们进行了一项全基因组关联研究，以确定单核苷酸多态性（SNP）与乳腺癌患者对蒽环类和紫杉烷为基础的新辅助化疗的反应。在发现阶段，我们根据病理反应将92例接受蒽环类药物新辅助化疗的患者分为2组，并使用Affyphase SNP 6.0基因芯片进行了全基因组研究。在与病理完全缓解（pCR）相关的389，795个SNP中，我们确定了2个SNP，rs6044100和rs 1799937，它们与新辅助化疗后的pCR显著相关。在验证阶段，使用测序分析对来自401名接受基于蒽环类药物的新辅助治疗方案的患者和467名接受基于紫杉烷的治疗方案的患者的独立队列的样本进行基因型分析。我们发现，只有位于WT 1基因的SNP rs 1799937与蒽环类药物新辅助治疗后的pCR相关（AA vs GG;比值比[OR]，2.81; 95%置信区间[CI]，1.13-6.98; P < 0.05），但在紫杉烷为基础的新辅助治疗后未发生（AA vs GG; OR，0.85; 95% CI，0.36-2.04; P = 0.72）。这些结果表明，WT 1可能是基于蒽环类药物的乳腺癌新辅助治疗的潜在靶点。
Breast cancer is believed to result from the interplay of genetic and non-genetic risk factors, and individual genetic variation may influence the efficacy of chemotherapy. Here we conducted a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with response to anthracycline- and taxane-based neoadjuvant chemotherapy in breast cancer patients. In the discovery stage, we divided 92 patients who received anthracycline-based neoadjuvant chemotherapy into 2 groups according to pathologic response and performed a genome-wide study using Affymetrix SNP6.0 genechip. Of 389,795 SNPs associated with pathologic complete response (pCR), we identified 2 SNPs, rs6044100 and rs1799937, that were significantly associated with pCR after neoadjuvant chemotherapy. In the validation stage, genotype analysis of samples from an independent cohort of 401 patients who received anthracycline-based neoadjuvant regimens and 467 patients who received taxane-based regimens was performed using sequencing analysis. We found that only SNP rs1799937, located in the WT1 gene, was associated with pCR after anthracycline-based neoadjuvant therapy (AA vs GG; odds ratio [OR], 2.81; 95% confidence interval [CI], 1.13–6.98; P < 0.05) but not after taxane-based neoadjuvant therapy (AA vs GG; OR, 0.85; 95% CI, 0.36–2.04; P = 0.72). These results suggest that WT1 may be a potential target of anthracycline-based neoadjuvant therapy for breast cancer.