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    Cancer Cell. 2011 Feb 15;19(2):273-82. doi: 10.1016/j.ccr.2010.12.019.

    The MDM2 promoter SNP285C/309G haplotype diminishes Sp1 transcription factor binding and reduces risk for breast and ovarian cancer in Caucasians.

    Knappskog S, Bjørnslett M, Myklebust LM, Huijts PE, Vreeswijk MP, Edvardsen H, Guo Y, Zhang X, Yang M, Ylisaukko-Oja SK, Alhopuro P, Arola J, Tollenaar RA, van Asperen CJ, Seynaeve C, Staalesen V, Chrisanthar R, Løkkevik E, Salvesen HB, Evans DG, Newman WG, Lin D, Aaltonen LA, Børresen-Dale AL, Tell GS, Stoltenberg C, Romundstad P, Hveem K, Lillehaug JR, Vatten L, Devilee P, Dørum A, Lønning PE.

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    Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway.

    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.

    Copyright © 2011 Elsevier Inc. All rights reserved.

    PMID:
    21316605
    [PubMed - indexed for MEDLINE]

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