globalchange  > 气候减缓与适应
DOI: 10.1158/0008-5472.CAN-18-2726
WOS ID: WOS:000457394600011
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 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.

Citation statistics:
Document Type: 期刊论文
Appears in Collections:气候减缓与适应

Files in This Item:

There are no files associated with this item.

Affiliation: 1.Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med,Div Epidemiol, 221 Kirkland Hall, Nashville, TN 37235 USA
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
9.Haukeland Hosp, Dept Gynecol & Obstet, Bergen, Norway
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
46.Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark
47.Univ Copenhagen, Rigshosp, Dept Gynecol, Juliane Marie Ctr, Copenhagen, Denmark
48.BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada
49.Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada
50.Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC, Canada
51.Vancouver Gen Hosp, OVCARE, Vancouver Coastal Hlth Res Ctr, Vancouver, BC, Canada
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
54.Med Univ South Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA
55.Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA
56.Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands
57.Univ Copenhagen, Rigshosp, Dept Gynaecol, Copenhagen, Denmark
58.Univ Montreal, CHUM Res Ctr CRCHUM, Montreal, PQ, Canada
59.Univ Montreal, Dept Med Social & Prevent, Montreal, PQ, Canada
60.Univ Leuven, VIB Ctr Canc Biol, VIB, Dept Human Genet, Leuven, Belgium
61.Univ Leuven, Lab Translat Genet, Dept Human Genet, Leuven, Belgium
62.BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada
63.Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA
64.NYU, Langone Med Ctr, Laura & Isaac Pearlmutter Canc Ctr, Gynecol Oncol, New York, NY USA
65.Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Gynaecol, Nijmegen, Netherlands
66.Aichi Canc Ctr, Res Inst, Div Mol Med, Nagoya, Aichi, Japan
67.Nagoya Univ, Grad Sch Med, Dept Epidemiol, Nagoya, Aichi, Japan
68.Univ Hlth Network, Princess Margaret Hosp, Div Gynecol Oncol, Toronto, ON, Canada
69.Imperial Coll London, Dept Surg & Canc, London, England
70.Univ Glasgow, Beatson Inst Canc Res, Wolfson Wohl Canc Res Ctr, Inst Canc Sci, Glasgow, Lanark, Scotland
71.UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit, London, England
72.Womens Canc Res Ctr, Magee Womens Res Inst, Pittsburgh, PA USA
73.Hillman Canc Ctr, Pittsburgh, PA USA
74.Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA
75.H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA
76.Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA
77.Roswell Pk Canc Inst, Div Canc Prevent & Control, Buffalo, NY 14263 USA
78.Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, UTHlth, Houston, TX 77030 USA
79.Univ Helsinki, Helsinki Univ Hosp, Dept Obstet & Gynecol, Helsinki, Finland
80.Lund Univ, Clin Sci, Dept Canc Epidemiol, Lund, Sweden
81.Univ Utrecht, UMC Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands
82.Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea
83.Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea
84.Seoul Natl Univ, Canc Res Inst, Seoul, South Korea
85.Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA
86.Univ Southern Calif, Keck Sch Med, Norris Comprehen Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA
87.Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA
88.Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA
89.Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA
90.Univ New South Wales Sydney, Fac Med, Sch Womens & Childrens Hlth, Sydney, NSW, Australia
91.Garvan Inst Med Res, Kinghorn Canc Ctr, Sydney, NSW, Australia
92.Imperial Coll London, London, England
93.IARC, WHO, Nutrit & Metab Sect, Lyon, France
94.NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA
95.Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA
96.Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA
97.Hebei Med Univ, Hosp 4, Dept Obstet & Gynaecol, Shijiazhuang, Hebei, Peoples R China
98.Glasgow Royal Infirm, Dept Gynaecolo Oncol, Glasgow, Lanark, Scotland
99.Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA
100.Icahn Sch Med Mt Sinai, Dept Hlth Sci & Policy, New York, NY 10029 USA
101.Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA
102.Harvard Med Sch, Boston, MA USA
103.Univ S Florida, Coll Med, Epidemiol Ctr, Tampa, FL USA
104.Inst Canc Res, Div Genet & Epidemiol, London, England
105.Inst Canc Res, Div Breast Canc Res, London, England
106.Maria Sklodowska Curie Inst, Oncol Ctr, Dept Immunol, Warsaw, Poland
107.Canc Res Malaysia, Subang Jaya, Selangor, Malaysia
108.Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur, Malaysia
109.Harvard TH Chan Sch Publ Hlth, Res Inst, Boston, MA USA
110.Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
111.Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England
112.QIMR Berghofer Med Res Inst, Populat Hlth Dept, Brisbane, Qld, Australia
113.NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
114.Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA
115.Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA
116.Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA
117.Karolinska Inst, Inst Environm Med, Stockholm, Sweden
118.Uppsala Univ, Dept Surg Sci, Uppsala, Sweden
119.Univ Malaya, Med Ctr, Dept Obstet & Gynaecol, Kuala Lumpur, Malaysia
120.Hebei Med Univ, Hosp 4, Dept Mol Biol, Shijiazhuang, Hebei, Peoples R China
121.NCSR Demokritos, INRASTES, Mol Diagnos Lab, Athens, Greece
122.QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia

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
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Yang, Yaohua]'s Articles
[Wu, Lang]'s Articles
[Shu, Xiang]'s Articles
Similar articles in Baidu Scholar
[Yang, Yaohua]'s Articles
[Wu, Lang]'s Articles
[Shu, Xiang]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Yang, Yaohua]‘s Articles
[Wu, Lang]‘s Articles
[Shu, Xiang]‘s Articles
Related Copyright Policies
所有评论 (0)

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.