globalchange  > 气候减缓与适应
DOI: 10.1158/0008-5472.CAN-18-2726
WOS ID: WOS:000457394600011
Title:
Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk
Author: Yang, Yaohua1; Wu, Lang1; Shu, Xiang1; Lu, Yingchang1; Shu, Xiao-Ou1; Cai, Qiuyin1; Beeghly-Fadiel, Alicia1; Li, Bingshan2; Ye, Fei3; Berchuck, Andrew4; Anton-Culver, Hoda5; Banerjee, Susana6; Benitez, Javier7,8; Bjorge, Line9,10; Brenton, James D.11; Butzow, Ralf12; Campbell, Ian G.13,14; Chang-Claude, Jenny15,16; Chen, Kexin17; Cook, Linda S.18,19; Cramer, Daniel W.20,21,22; defazio, Anna23,24; Dennis, Joe25; Doherty, Jennifer A.26; Doerk, Thilo27; Eccles, Diana M.28; Edwards, Digna Velez29; Fasching, Peter A.30,31; Fortner, Renee T.15; Gayther, Simon A.32; Giles, Graham G.33,34,35; Glasspool, Rosalind M.36; Goode, Ellen L.37; Goodman, Marc T.38; Gronwald, Jacek39; Harris, Holly R.40,41; Heitz, Florian42,43; Hildebrandt, Michelle A.44; Hogdall, Estrid45,46; Hogdall, Claus K.47; Huntsman, David G.48,49,50,51,52; Kar, Siddhartha P.25; Karlan, Beth Y.53; Kelemen, Linda E.54,55; Kiemeney, Lambertus A.56; Kjaer, Susanne K.45,57; Koushik, Anita58,59; Lambrechts, Diether60,61; Le, Nhu D.62; Levine, Douglas A.63,64; Massuger, Leon F.65; Matsuo, Keitaro66,67; May, Taymaa68; McNeish, Iain A.69,70; Menon, Usha71; Modugno, Francesmary72,73,74; Monteiro, Alvaro N.75; Moorman, Patricia G.76; Moysich, Kirsten B.77; Ness, Roberta B.78; Nevanlinna, Heli79; Olsson, Hakan80; Onland-Moret, N. Charlotte81; Park, Sue K.82,83,84; Paul, James36; Pearce, Celeste L.85,86; Pejovic, Tanja87,88; Phelan, Catherine M.75; Pike, Malcolm C.86,89; Ramus, Susan J.90,91; Riboli, Elio92; Rodriguez-Antona, Cristina7,8; Romieu, Isabelle93; Sandler, Dale P.94; Schildkraut, Joellen M.95; Setiawan, Veronica W.96; Shan, Kang97; Siddiqui, Nadeem98; Sieh, Weiva99,100; Stampfer, Meir J.101,102; Sutphen, Rebecca103; Swerdlow, Anthony J.104,105; Szafron, Lukasz M.106; Teo, Soo Hwang107,108; Tworoger, Shelley S.75,109,110; Tyrer, Jonathan P.111; Webb, Penelope M.112; Wentzensen, Nicolas113; White, Emily114,115; Willett, Walter C.20,101,102,116; Wolk, Alicja117,118; Woo, Yin Ling119; Wu, Anna H.96; Yan, Li120; Yannoukakos, Drakoulis121; Chenevix-Trench, Georgia122; Sellers, Thomas A.75; Pharoah, Paul D. P.25,111; Zheng, Wei1; Long, Jirong1
Corresponding Author: Long, Jirong
Source Publication: CANCER RESEARCH
ISSN: 0008-5472
EISSN: 1538-7445
Publishing Year: 2019
Volume: 79, Issue:3, Pages:505-517
Language: 英语
WOS Keyword: SUSCEPTIBILITY LOCI ; WIDE ASSOCIATION ; DISEASE ; MAPT ; PROTEIN ; TISSUE ; GWAS ; IDENTIFICATION ; VARIANTS ; THERAPY
WOS Category: Oncology
WOS Research Area: Oncology
English Abstract:

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 x 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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Document Type: 期刊论文
Identifier: http://119.78.100.158/handle/2HF3EXSE/128710
Appears in Collections:气候减缓与适应

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2.Vanderbilt Univ, Vanderbilt Genet Inst, Dept Mol Physiol & Biophys, 221 Kirkland Hall, Nashville, TN 37235 USA
3.Vanderbilt Univ, Med Ctr, Dept Biostat, Div Canc Biostat, 221 Kirkland Hall, Nashville, TN 37235 USA
4.Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA
5.Univ Calif Irvine, Genet Epidemiol Res Instl, Dept Epidemiol, Irvine, CA USA
6.Royal Marsden Hosp, Gynaecol Unit, London, England
7.Spanish Natl Canc Res Ctr, CNIO, Human Canc Genet Programme, Madrid, Spain
8.CIBERER, Biomed Network Rare Dis, Madrid, Spain
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10.Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers CCBIO, Bergen, Norway
11.Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England
12.Univ Helsinki, Helsinki Univ Hosp, Dept Pathol, Helsinki, Finland
13.Peter MacCallum Canc Inst, Melbourne, Vic, Australia
14.Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
15.German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany
16.Univ Med Ctr Hamburg Eppendorf, UCCH, Canc Epidemiol Grp, Hamburg, Germany
17.Tianjin Med Univ Canc Inst & Hosp, Dept Epidemiol, Tianjin, Peoples R China
18.Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA
19.Alberta Hlth Serv, Dept Canc Epidemiol & Prevent Res, Calgary, AB, Canada
20.Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
21.Brigham & Womens Hosp, Obstetr & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA
22.Harvard Med Sch, Boston, MA USA
23.Univ Sydney, Westmead Inst Med Res, Ctr Canc Res, Sydney, NSW, Australia
24.Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia
25.Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England
26.Univ Utah, Dept Populat Hlth Sci, Huntsman Canc Inst, Salt Lake City, UT USA
27.Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany
28.Univ Southampton, Fac Med, Canc Sci Acad Unit, Southampton, Hants, England
29.Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Vanderbilt Genet Inst,Vanderbilt Epidemol Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA
30.Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA
31.Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Comprehens Canc Ctr ER EMN, Dept Gynecol & Obstet, Erlangen, Germany
32.Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA
33.Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia
34.Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia
35.Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia
36.Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland
37.Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA
38.Cedars Sinai Med Ctr, Canc Prevent & Genet Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA
39.Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland
40.Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA
41.Univ Washington, Dept Epidemiol, Seattle, WA USA
42.Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany
43.Huyssens Stiftung Knappschaft GmbH, Kliniken Essen Mitte Evang, Dept Gynecol & Gynecol Oncol, Essen, Germany
44.Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA
45.Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark
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50.Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC, Canada
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52.Univ British Columbia, Vancouver, BC, Canada
53.Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA
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93.IARC, WHO, Nutrit & Metab Sect, Lyon, France
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Recommended Citation:
Yang, Yaohua,Wu, Lang,Shu, Xiang,et al. Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk[J]. CANCER RESEARCH,2019-01-01,79(3):505-517
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