A genome-wide association study identifies WT1 variant with better response to 5-fluorouracil, pirarubicin and cyclophosphamide neoadjuvant chemotherapy in breast cancer patients

// Lina Wu 2, * , Lu Yao 1, * , Hong Zhang 2 , Tao Ouyang 1 , Jinfeng Li 1 , Tianfeng Wang 1 , Zhaoqing Fan 1 , Tie Fan 1 , Benyao Lin 1 , C. Cameron Yin 3 , Yuntao Xie 1 1 Breast Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital, Beijing, P. R. China 2 Central Laboratory, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital, Beijing, P. R. China 3 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors have contributed equally to this work Correspondence to: Yuntao Xie, e-mail: zlxyt2@bjmu.edu.cn Keywords: WT1, rs1799937, breast cancer, anthracycline, neoadjuvant chemotherapy Received: July 08, 2015      Accepted: October 30, 2015      Published: November 09, 2015 ABSTRACT 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.