A genome-wide association study identifies three novel genetic markers for response to tamoxifen: A prospective multicenter study

PloS One
Hiroshi OnishiHitoshi Zembutsu

Abstract

Although association studies of genetic variations with the clinical outcomes of breast cancer patients treated with tamoxifen have been reported, genetic factors which could determine individual response to tamoxifen are not fully clarified. We performed a genome-wide association study (GWAS) to identify novel genetic markers for response to tamoxifen. We prospectively collected 347 blood samples from patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. We used Ki-67 response in breast cancer tissues after preoperative short-term tamoxifen therapy as a surrogate marker for response to tamoxifen. We performed GWAS and genotype imputation using 275 patients, and an independent set of 72 patients was used for replication study. The combined result of GWAS and the replication study, and subsequent imputation analysis indicated possible association of three loci with Ki-67 response after tamoxifen therapy (rs17198973 on chromosome 4q34.3, rs4577773 on 6q12, and rs7087428 on 10p13, Pcombined = 5.69 x 10-6, 1.64 x 10-5, and 9.77 x 10-6, respectively). When patients were classified into three groups by the s...Continue Reading

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Citations

Jan 27, 2019·Journal of Cell Communication and Signaling·Yong-Chul KimMary L Cutler

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Methods Mentioned

BETA
biopsy
genotyping
PCA

Software Mentioned

R
EIGENSTRAT
SHAPEIT
PLINK

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