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Brooks JD , Cairns P , Shore RE , Klein CB , Wirgin I , Afanasyeva Y , Zeleniuch-Jacquotte A
DNA methylation in pre-diagnostic serum samples of breast cancer cases: Results of a nested case-control study
Cancer Epidemiology. 2010 Dec;34(6) :717-723
PMID: ISI:000285900400009    PMCID: PMC2956002   
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Abstract
Background: Promoter methylation of tumor suppressor genes is a frequent and early event in breast carcinogenesis. Paired tumor tissue and serum samples from women with breast cancer show that promoter methylation is detectable in both sample types, with good concordance. This suggests the potential for these serum markers to be used for breast cancer detection. Methods: The current study was a case-control study nested within the prospective New York University Women's Health Study cohort aimed to assess the ability of promoter methylation in serum to detect pre-clinical disease. Cases were women with blood samples collected within the 6 months preceding breast cancer diagnosis (n = 50). Each case was matched to 2 healthy cancer-free controls and 1 cancer-free control with a history of benign breast disease (BBD). Results: Promoter methylation analysis of four cancer-related genes: RASSF1A, GSTP1, APC and RAR beta 2, - was conducted using quantitative methylation-specific PCR. Results showed that the frequency of methylation was lower than expected among cases and higher than expected among controls. Methylation was detected in the promoter region of: RASSF1A in 22.0%, 22.9% and 17.2% of cases, BBD controls and healthy controls respectively; GSTP1 in 4%, 10.4% and 7.1% respectively; APC in 2.0%, 4.4% and 4.2% respectively and RAR beta 2 in 6.7%, 2.3% and 1.1% respectively. Conclusion: Methylation status of the four genes included in this study was unable to distinguish between cases and either control group. This study highlights some methodological issues to be addressed in planning prospective studies to evaluate methylation markers as diagnostic biomarkers. (C) 2010 Elsevier Ltd. All rights reserved.
Notes
Brooks, Jennifer D. Cairns, Paul Shore, Roy E. Klein, Catherine B. Wirgin, Isaac Afanasyeva, Yelena Zeleniuch-Jacquotte, Anne DOD [BC060891]; Susan G. Komen for the Cure [BCTR0707521, R01 CA098661]; National Cancer Institute Cancer Center [CA-016087, R01CA034588, R01CA098661]; National Institute of Environmental Health Sciences center [ES-000260]; NIH Early Detection Research Network [1 U01 CA111242]; National Cancer Institute [P30CA016087]; National Institute of Environmental Health Science [E5000260] Grant Support: JDB: DOD Pre-doctoral Training Grant BC060891. JDB, AZJ, CBK: Susan G. Komen for the Cure BCTR0707521, R01 CA098661, AZJ: National Cancer Institute Cancer Center Grant CA-016087, and the National Institute of Environmental Health Sciences center grant ES-000260. PC: NIH Early Detection Research Network 1 U01 CA111242. The authors thank the participants of the New York University Women's Health Study (NYUWHS) whose participation made this project possible. This work was primarily funded through the research grant BCTR0707521 from Susan G. Komen for the Cure. The NYUWHS is supported by research grants R01CA034588, R01CA098661, center grant P30CA016087 from the National Cancer Institute and the center grant E5000260 from the National Institute of Environmental Health Science. 50 Elsevier sci ltd; the boulevard, langford lane, kidlington, oxford ox5 1gb, oxon, england 702nc