STANDARD_NAME HOFFMAN_CLOCK_TARGETS_UP SYSTEMATIC_NAME M2063 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/HOFFMAN_CLOCK_TARGETS_UP NAMESPACE Human_RefSeq DESCRIPTION_BRIEF Genes up-regulated in MCF7 cells (breast cancer) upon knockdown of CLOCK [GeneID=9575] by RNAi that also belong to the highest confidence network (according to Ingenuity Pathway Analysis). DESCRIPTION_FULL The transcription factors responsible for maintaining circadian rhythm influence a variety of biological processes. Recently, it has been suggested that the core circadian genes may play a role in breast tumorigenesis, possibly by influencing hormone regulation or other pathways relevant to cancer. To evaluate this hypothesis, we conducted a genetic and epigenetic association study, as well as a transcriptional profiling array and a pathway-based network analysis. We report significant correlations between single nucleotide polymorphisms associated with the central circadian regulator CLOCK and breast cancer risk, with apparent effect modification by estrogen receptor/progesterone receptor status. We also found that hypermethylation in the CLOCK promoter reduced the risk of breast cancer, and lower levels of CLOCK expression were documented in healthy controls relative to normal or tumor tissue from patients with breast cancer. Finally, we silenced CLOCK in vitro and performed a whole-genome expression microarray and pathway analysis, which identified a cancer-relevant network of transcripts with altered expression following CLOCK gene knockdown. Our findings support the hypothesis that circadian genes influence tumorigenesis, and identify a set of circadian gene variants as candidate breast cancer susceptibility biomarkers. PMID 20124474 GEOID GSE17766 AUTHORS Hoffman AE,Yi CH,Zheng T,Stevens RG,Leaderer D,Zhang Y,Holford TR,Hansen J,Paulson J,Zhu Y CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 2: Fold change > 0 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS NM_000700,NM_001001547,NM_001075,NM_001076,NM_001077,NM_002228,NM_002415,NM_002546,NM_006896,NM_032208,XM_938885 GENE_SYMBOLS ANXA1,CD36,UGT2B10,UGT2B15,UGT2B17,JUN,MIF,TNFRSF11B,HOXA7,ANTXR1, FOUNDER_NAMES