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000142948 0247_ $$2doi$$a10.1158/0008-5472.CAN-18-2726
000142948 0247_ $$2pmid$$apmid:30559148
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000142948 0247_ $$2ISSN$$a0008-5472
000142948 0247_ $$2ISSN$$a0099-7013
000142948 0247_ $$2ISSN$$a0099-7374
000142948 0247_ $$2ISSN$$a1538-7445
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000142948 037__ $$aDKFZ-2019-00576
000142948 041__ $$aeng
000142948 082__ $$a610
000142948 1001_ $$aYang, Yaohua$$b0
000142948 245__ $$aGenetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk.
000142948 260__ $$aPhiladelphia, Pa.$$bAACR$$c2019
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000142948 520__ $$a: DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 × 10-7. Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. SIGNIFICANCE: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
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000142948 7001_ $$aWu, Lang$$b1
000142948 7001_ $$00000-0002-4129-9403$$aShu, Xiang$$b2
000142948 7001_ $$aLu, Yingchang$$b3
000142948 7001_ $$00000-0002-4129-9403$$aShu, Xiao-Ou$$b4
000142948 7001_ $$aCai, Qiuyin$$b5
000142948 7001_ $$aBeeghly-Fadiel, Alicia$$b6
000142948 7001_ $$aLi, Bingshan$$b7
000142948 7001_ $$aYe, Fei$$b8
000142948 7001_ $$aBerchuck, Andrew$$b9
000142948 7001_ $$aAnton-Culver, Hoda$$b10
000142948 7001_ $$aBanerjee, Susana$$b11
000142948 7001_ $$aBenitez, Javier$$b12
000142948 7001_ $$aBjørge, Line$$b13
000142948 7001_ $$00000-0002-5738-6683$$aBrenton, James D$$b14
000142948 7001_ $$aButzow, Ralf$$b15
000142948 7001_ $$aCampbell, Ian G$$b16
000142948 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b17$$udkfz
000142948 7001_ $$aChen, Kexin$$b18
000142948 7001_ $$aCook, Linda S$$b19
000142948 7001_ $$aCramer, Daniel W$$b20
000142948 7001_ $$00000-0003-0057-4744$$adeFazio, Anna$$b21
000142948 7001_ $$00000-0003-4591-1214$$aDennis, Joe$$b22
000142948 7001_ $$aDoherty, Jennifer A$$b23
000142948 7001_ $$aDörk, Thilo$$b24
000142948 7001_ $$aEccles, Diana M$$b25
000142948 7001_ $$aEdwards, Digna Velez$$b26
000142948 7001_ $$00000-0003-4885-8471$$aFasching, Peter A$$b27
000142948 7001_ $$0P:(DE-He78)74a6af8347ec5cbd4b77e562e10ca1f2$$aTurzanski-Fortner, Renée$$b28$$udkfz
000142948 7001_ $$aGayther, Simon A$$b29
000142948 7001_ $$00000-0003-4946-9099$$aGiles, Graham G$$b30
000142948 7001_ $$aGlasspool, Rosalind M$$b31
000142948 7001_ $$aGoode, Ellen L$$b32
000142948 7001_ $$aGoodman, Marc T$$b33
000142948 7001_ $$aGronwald, Jacek$$b34
000142948 7001_ $$00000-0002-2572-6727$$aHarris, Holly R$$b35
000142948 7001_ $$aHeitz, Florian$$b36
000142948 7001_ $$aHildebrandt, Michelle A$$b37
000142948 7001_ $$aHøgdall, Estrid$$b38
000142948 7001_ $$aHøgdall, Claus K$$b39
000142948 7001_ $$aHuntsman, David G$$b40
000142948 7001_ $$aKar, Siddhartha P$$b41
000142948 7001_ $$aKarlan, Beth Y$$b42
000142948 7001_ $$aKelemen, Linda E$$b43
000142948 7001_ $$00000-0002-2368-1326$$aKiemeney, Lambertus A$$b44
000142948 7001_ $$00000-0002-8347-1398$$aKjaer, Susanne K$$b45
000142948 7001_ $$00000-0001-5304-7660$$aKoushik, Anita$$b46
000142948 7001_ $$aLambrechts, Diether$$b47
000142948 7001_ $$aLe, Nhu D$$b48
000142948 7001_ $$aLevine, Douglas A$$b49
000142948 7001_ $$aMassuger, Leon F$$b50
000142948 7001_ $$aMatsuo, Keitaro$$b51
000142948 7001_ $$aMay, Taymaa$$b52
000142948 7001_ $$00000-0002-9387-7586$$aMcNeish, Iain A$$b53
000142948 7001_ $$00000-0003-3708-1732$$aMenon, Usha$$b54
000142948 7001_ $$aModugno, Francesmary$$b55
000142948 7001_ $$00000-0002-8448-4801$$aMonteiro, Alvaro N$$b56
000142948 7001_ $$aMoorman, Patricia G$$b57
000142948 7001_ $$aMoysich, Kirsten B$$b58
000142948 7001_ $$aNess, Roberta B$$b59
000142948 7001_ $$00000-0002-0916-2976$$aNevanlinna, Heli$$b60
000142948 7001_ $$aOlsson, Håkan$$b61
000142948 7001_ $$aOnland-Moret, N Charlotte$$b62
000142948 7001_ $$00000-0001-5002-9707$$aPark, Sue K$$b63
000142948 7001_ $$00000-0001-7367-5816$$aPaul, James$$b64
000142948 7001_ $$aPearce, Celeste L$$b65
000142948 7001_ $$aPejovic, Tanja$$b66
000142948 7001_ $$aPhelan, Catherine M$$b67
000142948 7001_ $$aPike, Malcolm C$$b68
000142948 7001_ $$00000-0003-0005-7798$$aRamus, Susan J$$b69
000142948 7001_ $$aRiboli, Elio$$b70
000142948 7001_ $$00000-0001-8750-7338$$aRodriguez-Antona, Cristina$$b71
000142948 7001_ $$aRomieu, Isabelle$$b72
000142948 7001_ $$00000-0002-6776-0018$$aSandler, Dale P$$b73
000142948 7001_ $$aSchildkraut, Joellen M$$b74
000142948 7001_ $$aSetiawan, Veronica W$$b75
000142948 7001_ $$aShan, Kang$$b76
000142948 7001_ $$aSiddiqui, Nadeem$$b77
000142948 7001_ $$aSieh, Weiva$$b78
000142948 7001_ $$aStampfer, Meir J$$b79
000142948 7001_ $$aSutphen, Rebecca$$b80
000142948 7001_ $$aSwerdlow, Anthony J$$b81
000142948 7001_ $$00000-0003-1670-0274$$aSzafron, Lukasz M$$b82
000142948 7001_ $$00000-0002-0444-590X$$aTeo, Soo Hwang$$b83
000142948 7001_ $$00000-0002-6986-7046$$aTworoger, Shelley S$$b84
000142948 7001_ $$aTyrer, Jonathan P$$b85
000142948 7001_ $$00000-0003-0733-5930$$aWebb, Penelope M$$b86
000142948 7001_ $$aWentzensen, Nicolas$$b87
000142948 7001_ $$aWhite, Emily$$b88
000142948 7001_ $$aWillett, Walter C$$b89
000142948 7001_ $$00000-0001-7387-6845$$aWolk, Alicja$$b90
000142948 7001_ $$aWoo, Yin Ling$$b91
000142948 7001_ $$aWu, Anna H$$b92
000142948 7001_ $$aYan, Li$$b93
000142948 7001_ $$aYannoukakos, Drakoulis$$b94
000142948 7001_ $$aChenevix-Trench, Georgia$$b95
000142948 7001_ $$aSellers, Thomas A$$b96
000142948 7001_ $$aPharoah, Paul D P$$b97
000142948 7001_ $$aZheng, Wei$$b98
000142948 7001_ $$aLong, Jirong$$b99
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