Early detection of breast cancer improves both morbidity and mortality outcomes of breast cancer. Mammography, though able to decrease breast cancer mortality rates, is less sensitive in some subgroups of women. A complementary screening tool that can be used along-side mammography, improving sensitivity in these subgroups, would be advantageous.
Promoter methylation of tumor-suppressor genes is a frequent and early event in breast carcinogenesis. Tumors release DNA into the circulation and analysis of paired tumor tissue and serum samples from women with breast cancer have found that promoter methylation is detectable in both sample types, with a high level of concordance. This suggests the potential for these markers to be used as a tool for early breast cancer detection.
This was a case-control study nested within the New York University Women's Health Study (NYUWHS) designed to assess the ability of promoter methylation detected in serum to detect pre-clinical disease. Cases in this study were women for whom a blood sample was collected within the six months preceding diagnosis (n=113). Cases were then matched to 2 healthy cancer-free controls and 1 cancer-free control with a history of benign breast disease (BBD).
Promoter methylation of four cancer-related genes: RASSF1A, GSTP1, APC and RARβ2, was conducted in 50 case-controls sets using quantitative methylation specific PCR (QMSP). Results of this analysis showed that the frequency of promoter methylation of all four genes was lower than expected among cases and higher than expected among controls. For RASSF1A, 22.0%, 22.9% and 17.2% of cases, BBD controls and healthy controls respectively were methylated; GSTP1, 4%, 10.4% and 7.1% respectively; APC, 2.0%, 4.4% and 4.2% respectively and RARβ2, 6.7%, 2.3% and 1.1% respectively.
Subsequent analysis addressed the issues surrounding the potential for false-positive and false-negative results and addressed the possible limitations of using QMSP for methylation analysis in prospective studies.
|Commitee:||Cairns, Paul, Klein, Cathy, Liu, Mengling, Shore, Roy E., Wirgin, Isaac|
|School:||New York University|
|Department:||Environmental Health Science|
|School Location:||United States -- New York|
|Source:||DAI-B 70/12, Dissertation Abstracts International|
|Keywords:||Breast cancer, DNA methylation, Early detection, Epigenetic markers, Serum|
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