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MDM2 SNP309 accelerates familial breast carcinogenesis independently of estrogen signaling
Marijke Wasielewski1, Jord H A Nagel, Cecile Brekelmans
1Department of Medical Oncology, Josephine Nefkens Institute, Erasmus University Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Abstract:
A single nucleotide polymorphism (SNP309T>G) in the intronic promoter of MDM2 was recently found to accelerate carcinogenesis in early-onset cancer cases. This cancer acceleration presumably was due to increased SP1 binding, resulting in enhanced MDM2 transcriptional activation by estrogens. We evaluated MDM2 SNP309 in 343 familial breast cancer cases with known mutation status for CHEK2 1100delC, BRCA1 and BRCA2. Cancer acceleration was indeed observed in early-onset familial breast cancer cases (diagnosed
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