DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility.
DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility.
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DOI：
10.1016/j.ejca.2017.01.014
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Herceg Z
中科院分区：
文献类型：
--
作者：
Ambatipudi S;Horvath S;Perrier F;Cuenin C;Hernandez-Vargas H;Le Calvez-Kelm F;Durand G;Byrnes G;Ferrari P;Bouaoun L;Sklias A;Chajes V;Overvad K;Severi G;Baglietto L;Clavel-Chapelon F;Kaaks R;Barrdahl M;Boeing H;Trichopoulou A;Lagiou P;Naska A;Masala G;Agnoli C;Polidoro S;Tumino R;Panico S;Dollé M;Peeters PHM;Onland-Moret NC;Sandanger TM;Nøst TH;Weiderpass E;Quirós JR;Agudo A;Rodriguez-Barranco M;Huerta Castaño JM;Barricarte A;Fernández AM;Travis RC;Vineis P;Muller DC;Riboli E;Gunter M;Romieu I;Herceg Z
绝大多数人类恶性肿瘤与衰老有关，年龄是癌症风险的强有力预测因素。最近，基于DNA甲基化的衰老标志物，即“表观遗传时钟”，与癌症风险因素有关。本研究旨在评估表观遗传时钟是否与乳腺癌风险易感性相关，并确定潜在的基于表观遗传学的风险分层生物标志物。在这里，我们使用Illumina HumanMethylation 450 K BeadChip阵列分析了嵌入欧洲癌症和营养前瞻性研究（EPIC）队列（n = 960）的巢式病例对照研究中的DNA甲基化变化，并使用Horvath年龄估计方法计算这些样本的表观遗传年龄。内在表观遗传年龄加速度（IEAA）估计为残差表观遗传年龄对实足年龄的回归。我们观察到IEAA与乳腺癌风险之间存在相关性（OR，1.04; 95%CI，1.007-1.076，P = 0.016）。IEAA增加一个单位与乳腺癌发生几率增加4%相关（OR，1.04; 95%CI，1.007-1.076）。基于绝经状态的分层分析显示，IEAA与绝经后乳腺癌的发生相关（OR，1.07; 95%CI，1.020-1.11，P = 0.003）。此外，全甲基化组分析显示，胞嘧啶-磷酸-鸟嘌呤（CpG）岛的平均DNA甲基化水平较高与乳腺癌发生风险增加相关（OR/1 SD = 1.20; 95% CI：1.03-1.40，P = 0.02），而非岛CpG的平均甲基化水平在癌症病例和对照之间无法区分。表观遗传年龄加速和CpG岛甲基化与乳腺癌易感性有微弱但统计学显著的相关性。
A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as ‘epigenetic clock’, has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. Here, we profiled DNA methylation changes in a nested case–control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007–1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007–1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020–1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03–1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility.
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影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
DOI：
10.1093/infdis/jiv277
发表时间：
2015-11-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Horvath S;Levine AJ
通讯作者：
Levine AJ
乳腺癌不一致同卵双胞胎的 DNA 甲基化分析将 DOK7 确定为新型表观遗传生物标志物。
影响因子：
4.7
作者：
Heyn H;Carmona FJ;Gomez A;Ferreira HJ;Bell JT;Sayols S;Ward K;Stefansson OA;Moran S;Sandoval J;Eyfjord JE;Spector TD;Esteller M
通讯作者：
Esteller M
影响因子：
5.7
作者：
Breitling LP;Saum KU;Perna L;Schöttker B;Holleczek B;Brenner H
通讯作者：
Brenner H
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J