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Analysis of ZNF350/ZBRK1 promoter variants and breast cancer susceptibility in non-BRCA1/2 French Canadian breast cancer families.
MedLine Citation:
PMID:  23151675     Owner:  NLM     Status:  Publisher    
ZNF350/ZBRK1 is a transcription factor, which associates with BRCA1 to co-repress GADD45A to regulate DNA damage repair, and the expression of ZNF350 is altered in different human carcinomas. In a previous study, we identified ZNF350 genomic variants potentially involved in breast cancer susceptibility in high-risk non-BRCA1/2 breast cancer individuals, which pointed toward a potential association for variants in the 5'-UTR and promoter regions. Therefore, direct sequencing was undertaken and identified 12 promoter variants, whereas haplotype analyses put in evidence four common haplotypes with a frequency>2%. However, based on their frequency observed in breast cancer and unrelated healthy individuals, these are not statistically associated with breast cancer risk. Luciferase promoter assays in two breast cancer cell lines identified two haplotypes (H11 and H12) stimulating significantly the expression of ZNF350 transcript compared with the common haplotype H8. The high expression of the H11 allele was associated with the variant c.-874A. Using MatInspector and Transcription Element Search softwares, in silico analyses predicted that the variant c.-874A created a binding site for the factors c-Myc and myogenin. This study represents the first characterization step of the ZNF350 promoter. Additional studies in larger cohorts and other populations will be needed to further evaluate whether common and/or rare ZNF350 promoter variants and haplotypes could be associated with a modest risk of breast cancer.Journal of Human Genetics advance online publication, 15 November 2012; doi:10.1038/jhg.2012.127.
Karine V Plourde; Yvan Labrie; Sylvie Desjardins; Pascal Belleau; Geneviève Ouellette; Francine Durocher;
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-15
Journal Detail:
Title:  Journal of human genetics     Volume:  -     ISSN:  1435-232X     ISO Abbreviation:  J. Hum. Genet.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9808008     Medline TA:  J Hum Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Cancer Genomics Laboratory, Oncology and Molecular Endocrinology Research Centre, Centre Hospitalier Universitaire de Québec and Laval University, Québec city, QC, Canada.
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