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01-05-2009 | Epidemiology

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

Authors: Xinran Xu, Marilie D. Gammon, Yujing Zhang, Timothy H. Bestor, Steven H. Zeisel, James G. Wetmur, Sylvan Wallenstein, Patrick T. Bradshaw, Gail Garbowski, Susan L. Teitelbaum, Alfred I. Neugut, Regina M. Santella, Jia Chen

Published in: Breast Cancer Research and Treatment | Issue 2/2009

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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Title: BRCA1 promoter methylation is associated with increased mortality among women with breast cancer
Authors: Xinran Xu
Marilie D. Gammon
Yujing Zhang
Timothy H. Bestor
Steven H. Zeisel
James G. Wetmur
Sylvan Wallenstein
Patrick T. Bradshaw
Gail Garbowski
Susan L. Teitelbaum
Alfred I. Neugut
Regina M. Santella
Jia Chen
Publication date: 01-05-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0075-5

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