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Associating GWAS Information with the Notch Signaling Pathway Using Transcription Profiling

Genome-wide association studies (GWAS) have identified SNPs associated with breast cancer. However, they offer limited insights about the biological mechanisms by which SNPs confer risk. We investigated the association of GWAS information with a major oncogenic pathway in breast cancer, the Notch si...

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Detalles Bibliográficos
Autores principales: Hicks, Chindo, Pannuti, Antonio, Miele, Lucio
Formato: Texto
Lenguaje:English
Publicado: Libertas Academica 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091413/
https://www.ncbi.nlm.nih.gov/pubmed/21584266
http://dx.doi.org/10.4137/CIN.S6072
Descripción
Sumario:Genome-wide association studies (GWAS) have identified SNPs associated with breast cancer. However, they offer limited insights about the biological mechanisms by which SNPs confer risk. We investigated the association of GWAS information with a major oncogenic pathway in breast cancer, the Notch signaling pathway. We first identified 385 SNPs and 150 genes associated with risk for breast cancer by mining data from 41 GWAS. We then investigated their expression, along with 32 genes involved in the Notch signaling pathway using two publicly available gene expression data sets from the Caucasian (42 cases and 143 controls) and Asian (43 cases and 43 controls) populations. Pathway prediction and network modeling confirmed that Notch receptors and genes involved in the Notch signaling pathway interact with genes containing SNPs associated with risk for breast cancer. Additionally, we identified other SNP-associated biological pathways relevant to breast cancer, including the P53, apoptosis and MAP kinase pathways.