DNA Methylation Array Analysis Identifies Profiles of Blood-Derived DNA Methylation Associated With Bladder Cancer
DNA Methylation Array Analysis Identifies Profiles of Blood-Derived DNA Methylation Associated With Bladder Cancer
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DOI：
10.1200/jco.2010.31.3577
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发表时间：
2011-03-20
影响因子：
45.3
通讯作者：
Kelsey, Karl T.
中科院分区：
文献类型：
--
作者：
Marsit, Carmen J.;Koestler, Devin C.;Kelsey, Karl T.
目的肿瘤靶向组织中的表观遗传学改变在肿瘤的发生中起着因果作用。非靶组织，特别是外周血中DNA甲基化的变化也会影响患恶性疾病的风险。我们试图确定外周血中与膀胱癌风险相关的特定DNA甲基化特征，从而作为疾病易感性的表观遗传学标志。方法我们对参与一项基于人群的膀胱癌事件病例对照研究的参与者进行了全基因组DNA甲基化分析。结果在112例患者和118名对照的训练集中，我们在111例患者和119名对照的掩蔽独立测试系列中确定了9个CpG基因座的DNA甲基化特征与膀胱癌显著相关(P<；0.0001)。甲基化程度最高的三个类别的成员与膀胱癌风险增加5.2倍相关(95%CI，2.8至9.7)，包括甲基化分类、参与者年龄、性别、吸烟状况和膀胱癌家族史的模型是膀胱癌的显著预测因素(曲线下面积，0.76；95%CI，0.70至0.82)。与膀胱癌和衰老相关的CpG基因座的邻近序列富含与免疫调节和叉头家族成员相关的转录因子结合位点。结论这些结果表明血液中表观遗传状态的特征与膀胱癌的风险相关，并表明外周血中的表观遗传特征作为膀胱癌和其他恶性肿瘤易感性的新标记具有潜在的应用价值。J Clin Oncol29：1133-1139。(C)2011年美国临床肿瘤学会
PurposeEpigenetic alterations in tissues targeted for cancer play a causal role in carcinogenesis. Changes in DNA methylation in nontarget tissues, specifically peripheral blood, can also affect risk of malignant disease. We sought to identify specific profiles of DNA methylation in peripheral blood that are associated with bladder cancer risk and therefore serve as an epigenetic marker of disease susceptibility.MethodsWe performed genome-wide DNA methylation profiling on participants involved in a population-based incident case-control study of bladder cancer.ResultsIn a training set of 112 cases and 118 controls, we identified a panel of 9 CpG loci whose profile of DNA methylation was significantly associated with bladder cancer in a masked, independent testing series of 111 cases and 119 controls (P < .0001). Membership in three of the most methylated classes was associated with a 5.2-fold increased risk of bladder cancer (95% CI, 2.8 to 9.7), and a model that included the methylation classification, participant age, sex, smoking status, and family history of bladder cancer was a significant predictor of bladder cancer (area under the curve, 0.76; 95% CI, 0.70 to 0.82). CpG loci associated with bladder cancer and aging had neighboring sequences enriched for transcription-factor binding sites related to immune modulation and forkhead family members.ConclusionThese results indicate that profiles of epigenetic states in blood are associated with risk of bladder cancer and signal the potential utility of epigenetic profiles in peripheral blood as novel markers of susceptibility to this and other malignancies. J Clin Oncol 29: 1133-1139. (C) 2011 by American Society of Clinical Oncology