Hartmaier, Ryan J. and Tchatchou, Sandrine and Richter, Alexandra S. and Wang, Jay and McGuire, Sean E. and Skaar, Todd C. and Rae, Jimmy M. and Hemminki, Kari and Sutter, Christian and Ditsch, Nina and Bugert, Peter and Weber, Bernhard H. F. and Niederacher, Dieter and Arnold, Norbert and Varon-Mateeva, Raymonda and Wappenschmidt, Barbara and Schmutzler, Rita K. and Meindl, Alfons and Bartram, Claus R. and Burwinkel, Barbara and Oesterreich, Steffi (2009) Nuclear receptor coregulator SNP discovery and impact on breast cancer risk. BMC CANCER, 9: 438. ISSN 1471-2407,
Full text not available from this repository. (Request a copy)Abstract
Background: Coregulator proteins are "master regulators", directing transcriptional and posttranscriptional regulation of many target genes, and are critical in many normal physiological processes, but also in hormone driven diseases, such as breast cancer. Little is known on how genetic changes in these genes impact disease development and progression. Thus, we set out to identify novel single nucleotide polymorphisms (SNPs) within SRC-1 (NCoA1), SRC-3 (NCoA3, AIB1), NCoR (NCoR1), and SMRT (NCoR2), and test the most promising SNPs for associations with breast cancer risk. Methods: The identification of novel SNPs was accomplished by sequencing the coding regions of these genes in 96 apparently normal individuals (48 Caucasian Americans, 48 African Americans). To assess their association with breast cancer risk, five SNPs were genotyped in 1218 familial BRCA1/2-mutation negative breast cancer cases and 1509 controls (rs1804645, rs6094752, rs2230782, rs2076546, rs2229840). Results: Through our resequencing effort, we identified 74 novel SNPs (30 in NCoR, 32 in SMRT, 10 in SRC-3, and 2 in SRC-1). Of these, 8 were found with minor allele frequency (MAF) >5% illustrating the large amount of genetic diversity yet to be discovered. The previously shown protective effect of rs2230782 in SRC-3 was strengthened (OR = 0.45 [0.21-0.98], p = 0.04). No significant associations were found with the other SNPs genotyped. Conclusions: This data illustrates the importance of coregulators, especially SRC-3, in breast cancer development and suggests that more focused studies, including functional analyses, should be conducted.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ESTROGEN-RECEPTOR; HUMAN GENOME; SRC-1; COACTIVATOR; ASSOCIATION; GENE; POLYMORPHISMS; DISEASE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Aug 2020 09:36 |
| Last Modified: | 27 Aug 2020 09:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27979 |
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