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@article{Yang:2019:10.1158/0008-5472.CAN-18-2726,
author = {Yang, Y and Wu, L and Shu, X and Lu, Y and Shu, X-O and Cai, Q and Beeghly-Fadiel, A and Li, B and Ye, F and Berchuck, A and Anton-Culver, H and Banerjee, S and Benitez, J and Bjørge, L and Brenton, JD and Butzow, R and Campbell, IG and Chang-Claude, J and Chen, K and Cook, LS and Cramer, DW and DeFazio, A and Dennis, J and Doherty, JA and Dork, T and Eccles, DM and Velez, Edwards D and Fasching, PA and Fortner, RT and Gayther, SA and Giles, GG and Glasspool, RM and Goode, EL and Goodman, MT and Gronwald, J and Harris, HR and Heitz, F and Hildebrandt, MAT and Høgdall, E and Høgdall, CK and Huntsman, DG and Kar, SP and Karlan, BY and Kelemen, LE and Kiemeney, LA and Kjaer, SK and Koushik, A and Lambrechts, D and Le, ND and Levine, DA and Massuger, LFAG and Matsuo, K and May, T and McNeish, IA and Menon, U and Modugno, F and Monteiro, AN and Moorman, PG and Moysich, KB and Ness, RB and Nevanlinna, H and Olsson, H and Onland-Moret, NC and Park, SK and Paul, J and Pearce, CL and Pejovic, T},
doi = {10.1158/0008-5472.CAN-18-2726},
journal = {Cancer Research},
pages = {505--517},
title = {Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk},
url = {http://dx.doi.org/10.1158/0008-5472.CAN-18-2726},
volume = {79},
year = {2019}
}

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TY  - JOUR
AB  - 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.
AU  - Yang,Y
AU  - Wu,L
AU  - Shu,X
AU  - Lu,Y
AU  - Shu,X-O
AU  - Cai,Q
AU  - Beeghly-Fadiel,A
AU  - Li,B
AU  - Ye,F
AU  - Berchuck,A
AU  - Anton-Culver,H
AU  - Banerjee,S
AU  - Benitez,J
AU  - Bjørge,L
AU  - Brenton,JD
AU  - Butzow,R
AU  - Campbell,IG
AU  - Chang-Claude,J
AU  - Chen,K
AU  - Cook,LS
AU  - Cramer,DW
AU  - DeFazio,A
AU  - Dennis,J
AU  - Doherty,JA
AU  - Dork,T
AU  - Eccles,DM
AU  - Velez,Edwards D
AU  - Fasching,PA
AU  - Fortner,RT
AU  - Gayther,SA
AU  - Giles,GG
AU  - Glasspool,RM
AU  - Goode,EL
AU  - Goodman,MT
AU  - Gronwald,J
AU  - Harris,HR
AU  - Heitz,F
AU  - Hildebrandt,MAT
AU  - Høgdall,E
AU  - Høgdall,CK
AU  - Huntsman,DG
AU  - Kar,SP
AU  - Karlan,BY
AU  - Kelemen,LE
AU  - Kiemeney,LA
AU  - Kjaer,SK
AU  - Koushik,A
AU  - Lambrechts,D
AU  - Le,ND
AU  - Levine,DA
AU  - Massuger,LFAG
AU  - Matsuo,K
AU  - May,T
AU  - McNeish,IA
AU  - Menon,U
AU  - Modugno,F
AU  - Monteiro,AN
AU  - Moorman,PG
AU  - Moysich,KB
AU  - Ness,RB
AU  - Nevanlinna,H
AU  - Olsson,H
AU  - Onland-Moret,NC
AU  - Park,SK
AU  - Paul,J
AU  - Pearce,CL
AU  - Pejovic,T
AU  - Phelan,CM
AU  - Pike,MC
AU  - Ramus,SJ
AU  - Riboli,E
AU  - Rodríguez-Antona,C
AU  - Romieu,I
AU  - Sandler,DP
AU  - Schildkraut,JM
AU  - Setiawan,VW
AU  - Shan,K
AU  - Siddiqui,N
AU  - Sieh,W
AU  - Stampfer,MJ
AU  - Sutphen,R
AU  - Swerdlow,AJ
AU  - Szafron,LM
AU  - Teo,SH
AU  - Tworoger,SS
AU  - Tyrer,JP
AU  - Webb,PM
AU  - Wentzensen,N
AU  - White,E
AU  - Willett,WC
AU  - Wolk,A
AU  - Woo,YL
AU  - Wu,AH
AU  - Yan,L
AU  - Yannoukakos,D
AU  - Chenevix-Trench,G
AU  - Sellers,TA
AU  - Pharoah,PDP
AU  - Zheng,W
AU  - Long,J
DO  - 10.1158/0008-5472.CAN-18-2726
EP  - 517
PY  - 2019///
SN  - 1538-7445
SP  - 505
TI  - Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk
T2  - Cancer Research
UR  - http://dx.doi.org/10.1158/0008-5472.CAN-18-2726
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30559148
UR  - http://hdl.handle.net/10044/1/65342
VL  - 79
ER  -

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