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The MDM2 promoter SNP285C/309G haplotype diminishes Sp1 transcription factor binding and reduces risk for breast and ovarian cancer in Caucasians.
- Source :
-
Cancer cell [Cancer Cell] 2011 Feb 15; Vol. 19 (2), pp. 273-82. - Publication Year :
- 2011
-
Abstract
- MDM2 plays a key role in modulating p53 function. The MDM2 SNP309T > G promoter polymorphism enhances Sp1 binding and has been linked to cancer risk and young age at diagnosis although with conflicting evidence. We report a second MDM2 promoter polymorphism, SNP285G > C, residing on the SNP309G allele. SNP285C occurs in Caucasians only, where 7.7% (95% CI 7.6%-7.8%) of healthy individuals carry the SNP285C/309G haplotype. In vitro analyses reveals that SNP309G enhances but SNP285C strongly reduces Sp1 promoter binding. Comparing MDM2 promoter status among different cohorts of ovarian (n = 1993) and breast (n = 1973) cancer patients versus healthy controls (n = 3646), SNP285C reduced the risk of both ovarian (OR 0.74; CI 0.58-0.94) and breast cancer (OR 0.79; CI 0.62-1.00) among SNP309G carriers.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Case-Control Studies
Cohort Studies
Female
Humans
Protein Binding
Receptors, Estrogen metabolism
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
Breast Neoplasms genetics
Genetic Predisposition to Disease
Haplotypes
Ovarian Neoplasms genetics
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Proto-Oncogene Proteins c-mdm2 genetics
Sp1 Transcription Factor metabolism
White People
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3686
- Volume :
- 19
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 21316605
- Full Text :
- https://doi.org/10.1016/j.ccr.2010.12.019