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BRCA1 promoter methylation is associated with increased mortality among women with breast cancer

  • Epidemiology
  • Published:
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Abstract

Promoter-CpG island hypermethylation has been proposed as an alternative mechanism to inactivate BRCA1 in the breast where somatic mutations of BRCA1 are rare. To better understand breast cancer etiology and progression, we explored the association between BRCA1 promoter methylation status and prognostic factors as well as survival among women with breast cancer. Promoter methylation of BRCA1 was assessed in 851 archived tumor tissues collected from a population-based study of women diagnosed with invasive or in situ breast cancer in 1996–1997, and who were followed for vital status through the end of 2002. About 59% of the tumors were methylated at the promoter of BRCA1. The BRCA1 promoter methylation was more frequent in invasive cancers (P = 0.02) and among premenopausal cases (P = 0.05). BRCA1 promoter methylation was associated with increased risk of breast cancer-specific mortality (age-adjusted HR 1.71; 95% CI: 1.05–2.78) and all-cause mortality (age-adjusted HR 1.49; 95% CI: 1.02–2.18). Neither dietary methyl intakes in the year prior to the baseline interview nor the functional polymorphisms in one-carbon metabolism were associated with BRCA1 methylation status. Our study is the first epidemiological investigation on the prognostic value of BRCA1 promoter methylation in a large population-based cohort of breast cancer patients. Our results indicate that BRCA1 promoter methylation is an important factor to consider in predicting breast cancer survival.

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Author information

Authors and Affiliations

  1. Department of Community and Preventive Medicine, Mount Sinai School of Medicine, P.O. Box 1043, One Gustave L. Levy Place, New York, NY, 10029, USA

    Xinran Xu, Sylvan Wallenstein, Susan L. Teitelbaum & Jia Chen

  2. Department of Epidemiology, University of North Carolina, Chapel Hill, NC, 27599, USA

    Marilie D. Gammon & Patrick T. Bradshaw

  3. Department of Environmental Health Sciences, Columbia University, New York, NY, 10032, USA

    Yujing Zhang, Gail Garbowski & Regina M. Santella

  4. Department of Genetics and Development, Columbia University, New York, NY, 10032, USA

    Timothy H. Bestor

  5. Department of Nutrition, University of North Carolina, Chapel Hill, NC, 27599, USA

    Steven H. Zeisel

  6. Department of Microbiology, Mount Sinai School of Medicine, New York, NY, 10029, USA

    James G. Wetmur

  7. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, 10029, USA

    James G. Wetmur

  8. Department of Epidemiology, Columbia University, New York, NY, 10032, USA

    Alfred I. Neugut

  9. Department of Medicine, Columbia University, New York, NY, 10032, USA

    Alfred I. Neugut

  10. Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Jia Chen

  11. Department of Oncological Science, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Jia Chen

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  1. Xinran Xu
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Corresponding author

Correspondence to Jia Chen.

Additional information

This work was supported by grants from the National Institutes of Health (CA109753 to JC; DK55865 to SZ) and in part by grants from Department of Defense (BC031746), National Cancer Institute and the National Institutes of Environmental Health and Sciences (UO1CA/ES66572, UO1CA66572, P30CA013696, P30ES09089 and P30ES10126); and by the University of North Carolina Clinical Nutrition Research Unit (DK56350) and Center for Environmental Health and Susceptibility (ES10126). Xu, X. is a recipient of the Predoctoral Traineeship Award (W81XWH-06-1-0298) of Department of Defense Breast Cancer Research Program.

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Xu, X., Gammon, M.D., Zhang, Y. et al. BRCA1 promoter methylation is associated with increased mortality among women with breast cancer. Breast Cancer Res Treat 115, 397–404 (2009). https://doi.org/10.1007/s10549-008-0075-5

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