DNA methylation and cancer incidence: lymphatic-hematopoietic versus solid cancers in the Strong Heart Study.
DNA methylation and cancer incidence: lymphatic-hematopoietic versus solid cancers in the Strong Heart Study.
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DOI：
10.1186/s13148-021-01030-8
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发表时间：
2021-02-25
影响因子：
5.7
通讯作者：
Navas-Acien A
中科院分区：
文献类型：
--
作者：
Domingo-Relloso A;Huan T;Haack K;Riffo-Campos AL;Levy D;Fallin MD;Terry MB;Zhang Y;Rhoades DA;Herreros-Martinez M;Garcia-Esquinas E;Cole SA;Tellez-Plaza M;Navas-Acien A
表观遗传改变可能有助于癌症的早期发现。我们评估了血液DNA甲基化与淋巴-造血癌的关系，并与实体癌进行了比较。我们还评估了DNA甲基化对淋巴-造血癌的预测能力。使用Illumina Infinium甲基化EPIC阵列对2324名强心脏研究参与者(41.4%的男性，平均年龄56岁)进行了血液DNA甲基化检测。788,368个CpG位点可用于淋巴-造血癌、实体癌和全身癌的差异DNA甲基化分析，使用弹性网络和COX回归模型。我们在一个独立的人群中进行了复制：弗雷明翰心脏研究。我们还分析了差异变异性并进行了生物信息学分析，以评估潜在的生物学机制。在长达28年(平均15年)的随访中，我们发现了41例淋巴造血性癌症和394例实体癌。通过弹性网络模型选择了126个淋巴-造血性癌、396个实体癌和414个整体癌症的CPG作为预测因子。对于淋巴-造血癌，当将这126个CPG添加到发现集中的危险因素模型中时，预测能力(C指数)从0.58增加到0.87。在弗雷明翰心脏研究中，这种关联与28个CPGS中相同方向的风险比重复。当考虑可变性的关联，而不是平均差异时，我们发现淋巴-造血癌有432个差异可变区。这项研究表明，血液DNA甲基化的差异和差异变异性与淋巴-造血癌的风险有关。DNA甲基化数据可能有助于淋巴-造血癌的早期发现。
Epigenetic alterations may contribute to early detection of cancer. We evaluated the association of blood DNA methylation with lymphatic–hematopoietic cancers and, for comparison, with solid cancers. We also evaluated the predictive ability of DNA methylation for lymphatic–hematopoietic cancers. Blood DNA methylation was measured using the Illumina Infinium methylationEPIC array in 2324 Strong Heart Study participants (41.4% men, mean age 56 years). 788,368 CpG sites were available for differential DNA methylation analysis for lymphatic–hematopoietic, solid and overall cancers using elastic-net and Cox regression models. We conducted replication in an independent population: the Framingham Heart Study. We also analyzed differential variability and conducted bioinformatic analyses to assess for potential biological mechanisms. Over a follow-up of up to 28 years (mean 15), we identified 41 lymphatic–hematopoietic and 394 solid cancer cases. A total of 126 CpGs for lymphatic–hematopoietic cancers, 396 for solid cancers, and 414 for overall cancers were selected as predictors by the elastic-net model. For lymphatic–hematopoietic cancers, the predictive ability (C index) increased from 0.58 to 0.87 when adding these 126 CpGs to the risk factor model in the discovery set. The association was replicated with hazard ratios in the same direction in 28 CpGs in the Framingham Heart Study. When considering the association of variability, rather than mean differences, we found 432 differentially variable regions for lymphatic–hematopoietic cancers. This study suggests that differential methylation and differential variability in blood DNA methylation are associated with lymphatic–hematopoietic cancer risk. DNA methylation data may contribute to early detection of lymphatic–hematopoietic cancers.
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影响因子：
3
作者：
Abraham G;Kowalczyk A;Zobel J;Inouye M
通讯作者：
Inouye M
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
2.6
作者：
Hur, Ho;Lee, Ji-Yeon;Kim, Myoung Hee
通讯作者：
Kim, Myoung Hee
影响因子：
11.4
作者：
Deneberg, S.;Grovdal, M.;Lehmann, S.
通讯作者：
Lehmann, S.
影响因子：
78.8
作者：
Koch, Alexander;Joosten, Sophie C.;van Engeland, Manon
通讯作者：
van Engeland, Manon