Clinical Research Papers:
A genome-wide association study identifies WT1 variant with better response to 5-fluorouracil, pirarubicin and cyclophosphamide neoadjuvant chemotherapy in breast cancer patients
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Lina Wu2,*, Lu Yao1,*, Hong Zhang2, Tao Ouyang1, Jinfeng Li1, Tianfeng Wang1, Zhaoqing Fan1, Tie Fan1, Benyao Lin1, C. Cameron Yin3, Yuntao Xie1
1Breast Center, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital, Beijing, P. R. China
2Central Laboratory, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Cancer Hospital & Institute, Peking University Cancer Hospital, Beijing, P. R. China
3Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
*These authors have contributed equally to this work
Yuntao Xie, e-mail: [email protected]
Keywords: WT1, rs1799937, breast cancer, anthracycline, neoadjuvant chemotherapy
Received: July 08, 2015 Accepted: October 30, 2015 Published: November 09, 2015
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.
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