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Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk. / Yang, Yaohua; Wu, Lang; Shu, Xiang; Lu, Yingchang; Shu, Xiao Ou; Cai, Qiuyin; Beeghly-Fadiel, Alicia; Li, Bingshan; Ye, Fei; Berchuck, Andrew; Anton-Culver, Hoda; Banerjee, Susana; Benitez, Javier; Bjørge, Line; Brenton, James D.; Butzow, Ralf; Campbell, Ian G.; Chang-Claude, Jenny; Chen, Kexin; Cook, Linda S.; Cramer, Daniel W.; De Fazio, Anna; Dennis, Joe; Doherty, Jennifer A.; Eccles, Diana M.; Edwards, Digna Velez; Fasching, Peter A.; Fortner, Reneé T.; Gayther, Simon A.; Giles, Graham G.; Glasspool, Rosalind M.; Goode, Ellen L.; Goodman, Marc T.; Gronwald, Jacek; Harris, Holly R.; Heitz, Florian; Hildebrandt, Michelle A.; Høgdall, Estrid; Høgdall, Claus K.; Huntsman, David G.; Kar, Siddhartha P.; Karlan, Beth Y.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kjaer, Susanne K.; Koushik, Anita; Lambrechts, Diether; Le, Nhu D.; Levine, Douglas A.; Massuger, Leon F.; Matsuo, Keitaro; May, Taymaa; McNeish, Iain A.; Menon, Usha; Modugno, Francesmary; Monteiro, Alvaro N.; Moorman, Patricia G.; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Olsson, Håkan; Charlotte Onland-Moret, N.; Park, Sue K.; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Phelan, Catherine M.; Pike, Malcolm C.; Ramus, Susan J.; Riboli, Elio; Rodriguez-Antona, Cristina; Romieu, Isabelle; Sandler, Dale P.; Schildkraut, Joellen M.; Setiawan, Veronica W.; Shan, Kang; Siddiqui, Nadeem; Sieh, Weiva; Stampfer, Meir J.; Sutphen, Rebecca; Swerdlow, Anthony J.; Szafron, Lukasz M.; Teo, Soo Hwang; Tworoger, Shelley S.; Tyrer, Jonathan P.; Webb, Penelope M.; Wentzensen, Nicolas; White, Emily; Willett, Walter C.; Wolk, Alicja; Woo, Yin Ling; Wu, Anna H.; Yan, Li; Yannoukakos, Drakoulis; Chenevix-Trench, Georgia; Sellers, Thomas A.; Pharoah, Paul D.P.; Zheng, Wei; Long, Jirong.
I:
Cancer Research, Bind 79, Nr. 3, 2019, s. 505-517.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Yang, Y, Wu, L, Shu, X, Lu, Y, Shu, XO, Cai, Q, Beeghly-Fadiel, A, Li, B, Ye, F, Berchuck, A, Anton-Culver, H, Banerjee, S, Benitez, J, Bjørge, L, Brenton, JD, Butzow, R, Campbell, IG, Chang-Claude, J, Chen, K, Cook, LS, Cramer, DW, De Fazio, A, Dennis, J, Doherty, JA, Eccles, DM, Edwards, DV, Fasching, PA, Fortner, RT, Gayther, SA, Giles, GG, Glasspool, RM, Goode, EL, Goodman, MT, Gronwald, J, Harris, HR, Heitz, F, Hildebrandt, MA
, Høgdall, E, Høgdall, CK, Huntsman, DG, Kar, SP, Karlan, BY, Kelemen, LE, Kiemeney, LA
, Kjaer, SK, Koushik, A, Lambrechts, D, Le, ND, Levine, DA, Massuger, LF, Matsuo, K, May, T, McNeish, IA, Menon, U, Modugno, F, Monteiro, AN, Moorman, PG, Moysich, KB, Ness, RB, Nevanlinna, H, Olsson, H, Charlotte Onland-Moret, N, Park, SK, Paul, J, Pearce, CL, Pejovic, T, Phelan, CM, Pike, MC, Ramus, SJ, Riboli, E, Rodriguez-Antona, C, Romieu, I, Sandler, DP, Schildkraut, JM, Setiawan, VW, Shan, K, Siddiqui, N, Sieh, W, Stampfer, MJ, Sutphen, R, Swerdlow, AJ, Szafron, LM, Teo, SH, Tworoger, SS, Tyrer, JP, Webb, PM, Wentzensen, N, White, E, Willett, WC, Wolk, A, Woo, YL, Wu, AH, Yan, L, Yannoukakos, D, Chenevix-Trench, G, Sellers, TA, Pharoah, PDP, Zheng, W & Long, J 2019, '
Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk',
Cancer Research, bind 79, nr. 3, s. 505-517.
https://doi.org/10.1158/0008-5472.CAN-18-2726APA
Yang, Y., Wu, L., Shu, X., Lu, Y., Shu, X. O., Cai, Q., Beeghly-Fadiel, A., Li, B., Ye, F., Berchuck, A., Anton-Culver, H., Banerjee, S., Benitez, J., Bjørge, L., Brenton, J. D., Butzow, R., Campbell, I. G., Chang-Claude, J., Chen, K., ... Long, J. (2019).
Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk.
Cancer Research,
79(3), 505-517.
https://doi.org/10.1158/0008-5472.CAN-18-2726Vancouver
Yang Y, Wu L, Shu X, Lu Y, Shu XO, Cai Q o.a.
Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk.
Cancer Research. 2019;79(3):505-517.
https://doi.org/10.1158/0008-5472.CAN-18-2726Author
Yang, Yaohua ; Wu, Lang ; Shu, Xiang ; Lu, Yingchang ; Shu, Xiao Ou ; Cai, Qiuyin ; Beeghly-Fadiel, Alicia ; Li, Bingshan ; Ye, Fei ; Berchuck, Andrew ; Anton-Culver, Hoda ; Banerjee, Susana ; Benitez, Javier ; Bjørge, Line ; Brenton, James D. ; Butzow, Ralf ; Campbell, Ian G. ; Chang-Claude, Jenny ; Chen, Kexin ; Cook, Linda S. ; Cramer, Daniel W. ; De Fazio, Anna ; Dennis, Joe ; Doherty, Jennifer A. ; Eccles, Diana M. ; Edwards, Digna Velez ; Fasching, Peter A. ; Fortner, Reneé T. ; Gayther, Simon A. ; Giles, Graham G. ; Glasspool, Rosalind M. ; Goode, Ellen L. ; Goodman, Marc T. ; Gronwald, Jacek ; Harris, Holly R. ; Heitz, Florian ; Hildebrandt, Michelle A. ; Høgdall, Estrid ; Høgdall, Claus K. ; Huntsman, David G. ; Kar, Siddhartha P. ; Karlan, Beth Y. ; Kelemen, Linda E. ; Kiemeney, Lambertus A. ; Kjaer, Susanne K. ; Koushik, Anita ; Lambrechts, Diether ; Le, Nhu D. ; Levine, Douglas A. ; Massuger, Leon F. ; Matsuo, Keitaro ; May, Taymaa ; McNeish, Iain A. ; Menon, Usha ; Modugno, Francesmary ; Monteiro, Alvaro N. ; Moorman, Patricia G. ; Moysich, Kirsten B. ; Ness, Roberta B. ; Nevanlinna, Heli ; Olsson, Håkan ; Charlotte Onland-Moret, N. ; Park, Sue K. ; Paul, James ; Pearce, Celeste L. ; Pejovic, Tanja ; Phelan, Catherine M. ; Pike, Malcolm C. ; Ramus, Susan J. ; Riboli, Elio ; Rodriguez-Antona, Cristina ; Romieu, Isabelle ; Sandler, Dale P. ; Schildkraut, Joellen M. ; Setiawan, Veronica W. ; Shan, Kang ; Siddiqui, Nadeem ; Sieh, Weiva ; Stampfer, Meir J. ; Sutphen, Rebecca ; Swerdlow, Anthony J. ; Szafron, Lukasz M. ; Teo, Soo Hwang ; Tworoger, Shelley S. ; Tyrer, Jonathan P. ; Webb, Penelope M. ; Wentzensen, Nicolas ; White, Emily ; Willett, Walter C. ; Wolk, Alicja ; Woo, Yin Ling ; Wu, Anna H. ; Yan, Li ; Yannoukakos, Drakoulis ; Chenevix-Trench, Georgia ; Sellers, Thomas A. ; Pharoah, Paul D.P. ; Zheng, Wei ; Long, Jirong. / Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk. I: Cancer Research. 2019 ; Bind 79, Nr. 3. s. 505-517.
Bibtex
@article{fc276018617b4187ad7b494cfc921c05,
title = "Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk",
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 ¼ 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, ARH-GAP27, 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. ",
author = "Yaohua Yang and Lang Wu and Xiang Shu and Yingchang Lu and Shu, {Xiao Ou} and Qiuyin Cai and Alicia Beeghly-Fadiel and Bingshan Li and Fei Ye and Andrew Berchuck and Hoda Anton-Culver and Susana Banerjee and Javier Benitez and Line Bj{\o}rge and Brenton, {James D.} and Ralf Butzow and Campbell, {Ian G.} and Jenny Chang-Claude and Kexin Chen and Cook, {Linda S.} and Cramer, {Daniel W.} and {De Fazio}, Anna and Joe Dennis and Doherty, {Jennifer A.} and Eccles, {Diana M.} and Edwards, {Digna Velez} and Fasching, {Peter A.} and Fortner, {Rene{\'e} T.} and Gayther, {Simon A.} and Giles, {Graham G.} and Glasspool, {Rosalind M.} and Goode, {Ellen L.} and Goodman, {Marc T.} and Jacek Gronwald and Harris, {Holly R.} and Florian Heitz and Hildebrandt, {Michelle A.} and Estrid H{\o}gdall and H{\o}gdall, {Claus K.} and Huntsman, {David G.} and Kar, {Siddhartha P.} and Karlan, {Beth Y.} and Kelemen, {Linda E.} and Kiemeney, {Lambertus A.} and Kjaer, {Susanne K.} and Anita Koushik and Diether Lambrechts and Le, {Nhu D.} and Levine, {Douglas A.} and Massuger, {Leon F.} and Keitaro Matsuo and Taymaa May and McNeish, {Iain A.} and Usha Menon and Francesmary Modugno and Monteiro, {Alvaro N.} and Moorman, {Patricia G.} and Moysich, {Kirsten B.} and Ness, {Roberta B.} and Heli Nevanlinna and H{\aa}kan Olsson and {Charlotte Onland-Moret}, N. and Park, {Sue K.} and James Paul and Pearce, {Celeste L.} and Tanja Pejovic and Phelan, {Catherine M.} and Pike, {Malcolm C.} and Ramus, {Susan J.} and Elio Riboli and Cristina Rodriguez-Antona and Isabelle Romieu and Sandler, {Dale P.} and Schildkraut, {Joellen M.} and Setiawan, {Veronica W.} and Kang Shan and Nadeem Siddiqui and Weiva Sieh and Stampfer, {Meir J.} and Rebecca Sutphen and Swerdlow, {Anthony J.} and Szafron, {Lukasz M.} and Teo, {Soo Hwang} and Tworoger, {Shelley S.} and Tyrer, {Jonathan P.} and Webb, {Penelope M.} and Nicolas Wentzensen and Emily White and Willett, {Walter C.} and Alicja Wolk and Woo, {Yin Ling} and Wu, {Anna H.} and Li Yan and Drakoulis Yannoukakos and Georgia Chenevix-Trench and Sellers, {Thomas A.} and Pharoah, {Paul D.P.} and Wei Zheng and Jirong Long",
year = "2019",
doi = "10.1158/0008-5472.CAN-18-2726",
language = "English",
volume = "79",
pages = "505--517",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research",
number = "3",
}
RIS
TY - JOUR
T1 - Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk
AU - Yang, Yaohua
AU - Wu, Lang
AU - Shu, Xiang
AU - Lu, Yingchang
AU - Shu, Xiao Ou
AU - Cai, Qiuyin
AU - Beeghly-Fadiel, Alicia
AU - Li, Bingshan
AU - Ye, Fei
AU - Berchuck, Andrew
AU - Anton-Culver, Hoda
AU - Banerjee, Susana
AU - Benitez, Javier
AU - Bjørge, Line
AU - Brenton, James D.
AU - Butzow, Ralf
AU - Campbell, Ian G.
AU - Chang-Claude, Jenny
AU - Chen, Kexin
AU - Cook, Linda S.
AU - Cramer, Daniel W.
AU - De Fazio, Anna
AU - Dennis, Joe
AU - Doherty, Jennifer A.
AU - Eccles, Diana M.
AU - Edwards, Digna Velez
AU - Fasching, Peter A.
AU - Fortner, Reneé T.
AU - Gayther, Simon A.
AU - Giles, Graham G.
AU - Glasspool, Rosalind M.
AU - Goode, Ellen L.
AU - Goodman, Marc T.
AU - Gronwald, Jacek
AU - Harris, Holly R.
AU - Heitz, Florian
AU - Hildebrandt, Michelle A.
AU - Høgdall, Estrid
AU - Høgdall, Claus K.
AU - Huntsman, David G.
AU - Kar, Siddhartha P.
AU - Karlan, Beth Y.
AU - Kelemen, Linda E.
AU - Kiemeney, Lambertus A.
AU - Kjaer, Susanne K.
AU - Koushik, Anita
AU - Lambrechts, Diether
AU - Le, Nhu D.
AU - Levine, Douglas A.
AU - Massuger, Leon F.
AU - Matsuo, Keitaro
AU - May, Taymaa
AU - McNeish, Iain A.
AU - Menon, Usha
AU - Modugno, Francesmary
AU - Monteiro, Alvaro N.
AU - Moorman, Patricia G.
AU - Moysich, Kirsten B.
AU - Ness, Roberta B.
AU - Nevanlinna, Heli
AU - Olsson, Håkan
AU - Charlotte Onland-Moret, N.
AU - Park, Sue K.
AU - Paul, James
AU - Pearce, Celeste L.
AU - Pejovic, Tanja
AU - Phelan, Catherine M.
AU - Pike, Malcolm C.
AU - Ramus, Susan J.
AU - Riboli, Elio
AU - Rodriguez-Antona, Cristina
AU - Romieu, Isabelle
AU - Sandler, Dale P.
AU - Schildkraut, Joellen M.
AU - Setiawan, Veronica W.
AU - Shan, Kang
AU - Siddiqui, Nadeem
AU - Sieh, Weiva
AU - Stampfer, Meir J.
AU - Sutphen, Rebecca
AU - Swerdlow, Anthony J.
AU - Szafron, Lukasz M.
AU - Teo, Soo Hwang
AU - Tworoger, Shelley S.
AU - Tyrer, Jonathan P.
AU - Webb, Penelope M.
AU - Wentzensen, Nicolas
AU - White, Emily
AU - Willett, Walter C.
AU - Wolk, Alicja
AU - Woo, Yin Ling
AU - Wu, Anna H.
AU - Yan, Li
AU - Yannoukakos, Drakoulis
AU - Chenevix-Trench, Georgia
AU - Sellers, Thomas A.
AU - Pharoah, Paul D.P.
AU - Zheng, Wei
AU - Long, Jirong
PY - 2019
Y1 - 2019
N2 - 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 ¼ 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, ARH-GAP27, 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.
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 ¼ 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, ARH-GAP27, 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.
U2 - 10.1158/0008-5472.CAN-18-2726
DO - 10.1158/0008-5472.CAN-18-2726
M3 - Journal article
C2 - 30559148
AN - SCOPUS:85060947651
VL - 79
SP - 505
EP - 517
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 3
ER -
