1. The MDM2 Promoter SNP285C/309G Haplotype Diminishes Sp1 Transcription Factor Binding and Reduces Risk for Breast and Ovarian Cancer in Caucasians
- Author
-
Johanna Arola, William G. Newman, Camilla Stoltenberg, Ranjan Chrisanthar, Per Eystein Lønning, Caroline Seynaeve, Hege Edvardsen, Dongxin Lin, Grethe S. Tell, Maaike P.G. Vreeswijk, Christi J. van Asperen, Kristian Hveem, Line M. Myklebust, Ming Yang, Vidar Staalesen, Helga B. Salvesen, Stian Knappskog, Lauri A. Aaltonen, Anne Dørum, D. Gareth Evans, Xuemei Zhang, Lars J. Vatten, Pål Richard Romundstad, Rob A. E. M. Tollenaar, Sanna K. Ylisaukko-oja, Merete Bjørnslett, Erik Løkkevik, Anne Lise Børresen-Dale, Pia Alhopuro, Yongli Guo, Johan R. Lillehaug, Petra E A Huijts, Peter Devilee, and Medical Oncology
- Subjects
medicine.medical_specialty ,Cancer Research ,Sp1 Transcription Factor ,Breast Neoplasms ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,White People ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,SDG 3 - Good Health and Well-being ,Polymorphism (computer science) ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Promoter Regions, Genetic ,030304 developmental biology ,Ovarian Neoplasms ,0303 health sciences ,Haplotype ,Case-control study ,Cancer ,Proto-Oncogene Proteins c-mdm2 ,Cell Biology ,medicine.disease ,3. Good health ,Endocrinology ,Haplotypes ,Receptors, Estrogen ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,Tumor Suppressor Protein p53 ,Ovarian cancer ,Protein Binding - Abstract
SummaryMDM2 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.
- Published
- 2011