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- PMID: 21316605
- UKPMCID: 21316605
- DOI: 10.1016/j.ccr.2010.12.019
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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.
Knappskog, Stian; Bjørnslett, Merete; Myklebust, Line M; Huijts, Petra E A; Vreeswijk, Maaike P; Edvardsen, Hege; Guo, Yongli; Zhang, Xuemei; Yang, Ming; Ylisaukko-Oja, Sanna K; Alhopuro, Pia; Arola, Johanna; Tollenaar, Rob A E M; van Asperen, Christi J; Seynaeve, Caroline; Staalesen, Vidar; Chrisanthar, Ranjan; Løkkevik, Erik; Salvesen, Helga B; Evans, D Gareth; Newman, William G; Lin, Dongxin; Aaltonen, Lauri A; Børresen-Dale, Anne-Lise; Tell, Grethe S; Stoltenberg, Camilla; Romundstad, Pål; Hveem, Kristian; Lillehaug, Johan R; Vatten, Lars; Devilee, Peter; Dørum, Anne; Lønning, Per E
Cancer cell. 2011;19(2):273-82.
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Full-text held externally
- PMID: 21316605
- UKPMCID: 21316605
- DOI: 10.1016/j.ccr.2010.12.019
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.
Bibliographic metadata
- Knappskog, Stian
- Bjørnslett, Merete
- Myklebust, Line M
- Huijts, Petra E A
- Vreeswijk, Maaike P
- Edvardsen, Hege
- Guo, Yongli
- Zhang, Xuemei
- Yang, Ming
- Ylisaukko-Oja, Sanna K
- Alhopuro, Pia
- Arola, Johanna
- Tollenaar, Rob A E M
- van Asperen, Christi J
- Seynaeve, Caroline
- Staalesen, Vidar
- Chrisanthar, Ranjan
- Løkkevik, Erik
- Salvesen, Helga B
- Evans, D Gareth
- Newman, William G
- Lin, Dongxin
- Aaltonen, Lauri A
- Børresen-Dale, Anne-Lise
- Tell, Grethe S
- Stoltenberg, Camilla
- Romundstad, PĂĄl
- Hveem, Kristian
- Lillehaug, Johan R
- Vatten, Lars
- Devilee, Peter
- Dørum, Anne
- Lønning, Per E