title: Integrative Analysis of Response to Tamoxifen Treatment in ER-Positive Breast Cancer Using GWAS Information and Transcription Profiling.
abstract: Variable response and resistance to tamoxifen treatment in breast cancer patients remains a major clinical problem. To determine whether genes and biological pathways containing SNPs associated with risk for breast cancer are dysregulated in response to tamoxifen treatment, we performed analysis combining information from 43 genome-wide association studies with gene expression data from 298 ER(+) breast cancer patients treated with tamoxifen and 125 ER(+) controls. We identified 95 genes which distinguished tamoxifen treated patients from controls. Additionally, we identified 54 genes which stratified tamoxifen treated patients into two distinct groups. We identified biological pathways containing SNPs associated with risk for breast cancer, which were dysregulated in response to tamoxifen treatment. Key pathways identified included the apoptosis, P53, NFkB, DNA repair and cell cycle pathways. Combining GWAS with transcription profiling provides a unified approach for associating GWAS findings with response to drug treatment and identification of potential drug targets.
authors.affiliation: Cancer Institute, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216.
authors.forename: Chindo
authors.initials: C
authors.lastname: Hicks
authors.forename: Ranjit
authors.initials: R
authors.lastname: Kumar
authors.forename: Antonio
authors.initials: A
authors.lastname: Pannuti
authors.forename: Lucio
authors.initials: L
authors.lastname: Miele