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The p53 Arg72Pro and MDM2 -309 polymorphisms and risk of breast cancer in the nurses’ health studies

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Abstract

Candidate gene association studies to detect breast cancer susceptibility loci have yielded few positive associations. Therefore, it is more likely that variants in many genes along related biological pathways combine to influence breast cancer risk. A strong candidate pathway is that of p53-mediated cell-cycle control, DNA repair, and apoptosis. The two major proteins along this pathway are p53 and its negative regulator MDM2. Functional polymorphisms in both genes have been identified. The -309 SNP in MDM2 is associated with increased MDM2 transcription. The Arg72Pro polymorphism of p53 alters the transcription of p53 target genes and modifies the apoptotic potential of cells. Both polymorphisms have been studied with respect to breast cancer risk, with inconclusive results. We have genotyped both polymorphisms in the breast cancer cases and controls nested within the Nurses’ Health Study and Nurses’ Health Study II. Neither SNP is independently associated with overall breast cancer risk. Some indication of gene-by-gene interaction was observed; however, no consistent direction of interaction was apparent.

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Acknowledgments

We are indebted to the participants in the Nurses’ Health Study and Nurses’ Health Study II for their continuing dedication and commitment. The authors would like to thank the laboratory of Helena Judge-Ellis for blood sample storage and preparation, Patrice Soule for DNA extraction and plating, and Hardeep Ranu for TaqMan genotyping.

Supported by National Institutes of Health research grants CA87969 and CA65725. D.G.C. is supported by training grant CA09001-27 from the National Institutes of Health. I.D. is supported by research grants CA82838 from the National Institutes of Health and RSG-00-061-04-CCE from the American Cancer Society.

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Authors and Affiliations

  1. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    David G. Cox, Shelley S. Tworoger, Susan E. Hankinson, David J. Hunter & Immaculata De Vivo

  2. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    David G. Cox, Dwayne Deer, Qun Guo, Shelley S. Tworoger, David J. Hunter & Immaculata De Vivo

  3. Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, 677 Huntington Ave., Boston, MA, 02115, USA

    David G. Cox, David J. Hunter & Immaculata De Vivo

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  1. David G. Cox
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  2. Dwayne Deer
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  3. Qun Guo
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  4. Shelley S. Tworoger
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  5. Susan E. Hankinson
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  6. David J. Hunter
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  7. Immaculata De Vivo
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Correspondence to David G. Cox.

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Cox, D.G., Deer, D., Guo, Q. et al. The p53 Arg72Pro and MDM2 -309 polymorphisms and risk of breast cancer in the nurses’ health studies. Cancer Causes Control 18, 621–625 (2007). https://doi.org/10.1007/s10552-007-9004-x

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  • DOI: https://doi.org/10.1007/s10552-007-9004-x

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