MDM2 SNP309 accelerates familial breast carcinogenesis independently of estrogen signaling

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 e...

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Bibliographic Details
Published in:Breast cancer research and treatment 2007-08, Vol.104 (2), p.153-157
Main Authors: WASIELEWSKI, Marijke, NAGEL, Jord H. A, BREKELMANS, Cecile, KLIJN, Jan G. M, VAN DEN OUWELAND, Ans, MEIJERS-HEIJBOER, Hanne, SCHUTTE, Mieke
Format: Article
Language:English
Subjects:
Adult
Age
Biological and medical sciences
BRCA1 protein
BRCA2 protein
Breast
Breast cancer
Breast Neoplasms - genetics
Cancer research
Carcinogenesis
Case-Control Studies
Cell Transformation, Neoplastic
Epidemiology
Estrogen receptors
Estrogens
Estrogens - metabolism
Female
Gene polymorphism
Genes, BRCA1
Genes, BRCA2
Genetic Predisposition to Disease
Genotype & phenotype
Germ-Line Mutation
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
MDM2 protein
Medical sciences
Middle Aged
Mutants
Polymorphism
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-mdm2 - genetics
Risk Factors
Signal Transduction
Single-nucleotide polymorphism
Transcription activation
Tumors
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Description
Summary: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
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-006-9407-5