DNA methylation in pre-diagnostic serum samples of breast cancer cases: results of a nested case-control study.
DNA methylation in pre-diagnostic serum samples of breast cancer cases: results of a nested case-control study.
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DOI：
10.1016/j.canep.2010.05.006
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发表时间：
2010-12
影响因子：
2.6
通讯作者：
Zeleniuch-Jacquotte, Anne
中科院分区：
文献类型：
--
作者：
Brooks, Jennifer D.;Cairns, Paul;Shore, Roy E.;Klein, Catherine B.;Wirgin, Isaac;Afanasyeva, Yelena;Zeleniuch-Jacquotte, Anne
抑癌基因启动子甲基化是乳腺癌发生过程中常见的早期事件。配对的乳腺癌妇女的肿瘤组织和血清样本显示，启动子甲基化在两种样本类型中都可检测到，具有良好的一致性。这表明这些血清标志物有可能用于乳腺癌检测。目前的研究是一项病例对照研究，嵌套在前瞻性纽约大学妇女健康研究队列中，旨在评估血清中启动子甲基化检测临床前疾病的能力。病例为在乳腺癌诊断前6个月内采集血样的女性（n=50）。每个病例与2名健康的无癌对照和1名有良性乳腺疾病（BBD）史的无癌对照相匹配。采用甲基化特异性定量PCR技术对RASSF 1A、GSTP 1、APC和RARβ2 4个肿瘤相关基因的启动子甲基化进行分析。结果显示，甲基化的频率在病例中低于预期，在对照中高于预期。RASSF 1A基因启动子区甲基化率分别为22.0%、22.9%和17.2%，GST P1基因启动子区甲基化率分别为4%、10.4%和7.1%，APC基因启动子区甲基化率分别为2.0%、4.4%和4.2%，RARβ2基因启动子区甲基化率分别为6.7%、2.3%和1.1%。本研究中包括的四个基因的甲基化状态无法区分病例组和对照组。本研究强调了在计划前瞻性研究以评估甲基化标记物作为诊断生物标志物时需要解决的一些方法学问题。
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. 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 six 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). Promoter methylation analysis of four cancer-related genes: — RASSF1A, GSTP1, APC and RARβ2, — 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 RARβ2 in 6.7%, 2.3% and 1.1% respectively. 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.
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DOI：
10.1196/annals.1395.005
发表时间：
2007-01-01
期刊：
BIOGERONTOLOGY: MECHANISMS AND INTERVENTIONS
影响因子：
--
作者：
Fraga, Mario F.;Agrelo, Ruben;Esteller, Manel
通讯作者：
Esteller, Manel
DOI：
10.1073/pnas.0507904102
发表时间：
2005-11-08
影响因子：
11.1
作者：
Diehl, F;Li, M;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
6.1
作者：
Mirza, Sameer;Sharma, Gayatri;Ralhan, Ranju
通讯作者：
Ralhan, Ranju
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M
影响因子：
158.5
作者：
Elmore, G;Barton, MB;Fletcher, SW
通讯作者：
Fletcher, SW