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Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk

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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, JD, Butzow, R, Campbell, IG, Chang-Claude, J, Chen, K, Cook, LS, Cramer, DW, DeFazio, A, Dennis, J, Doherty, JA, Dork, T, Eccles, DM, Velez Edwards, D, Fasching, PA, Fortner, RT, Gayther, SA, Giles, GG, Glasspool, RM, Goode, EL, Goodman, MT, Gronwald, J, Harris, HR, Heitz, F, Hildebrandt, MAT, 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, LFAG, Matsuo, K, May, T, McNeish, IA, Menon, U, Modugno, F, Monteiro, AN, Moorman, PG, Moysich, KB, Ness, RB, Nevanlinna, H, Olsson, H, Onland-Moret, NC, Park, SK, Paul, J, Pearce, CL, Pejovic, T, Phelan, CM, Pike, MC, Ramus, SJ, Riboli, E, Rodríguez-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-18-2726

APA

CBE

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 JD, Butzow R, Campbell IG, Chang-Claude J, Chen K, Cook LS, Cramer DW, DeFazio A, Dennis J, Doherty JA, Dork T, Eccles DM, Velez Edwards D, Fasching PA, Fortner RT, Gayther SA, Giles GG, Glasspool RM, Goode EL, Goodman MT, Gronwald J, Harris HR, Heitz F, Hildebrandt MAT, 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 LFAG, Matsuo K, May T, McNeish IA, Menon U, Modugno F, Monteiro AN, Moorman PG, Moysich KB, Ness RB, Nevanlinna H, Olsson H, Onland-Moret NC, Park SK, Paul J, Pearce CL, Pejovic T, Phelan CM, Pike MC, Ramus SJ, Riboli E, Rodríguez-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. 79(3):505-517. https://doi.org/10.1158/0008-5472.CAN-18-2726

MLA

Vancouver

Author

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 ; DeFazio, Anna ; Dennis, Joe ; Doherty, Jennifer A ; Dork, Thilo ; Eccles, Diana M ; Velez Edwards, Digna ; Fasching, Peter A ; Fortner, Renée 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 T ; 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 A G ; 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 ; Onland-Moret, N Charlotte ; Park, Sue K ; Paul, James ; Pearce, Celeste L ; Pejovic, Tanja ; Phelan, Catherine M ; Pike, Malcolm C ; Ramus, Susan J ; Riboli, Elio ; Rodríguez-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 Michal ; 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{9fdcb557224443bba28595b16adb2008,
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 = 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.",
author = "Yaohua Yang and Lang Wu and Xiang Shu and Yingchang Lu and Xiao-Ou Shu 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 Anna DeFazio and Joe Dennis and Doherty, {Jennifer A} and Thilo Dork and Eccles, {Diana M} and {Velez Edwards}, Digna and Fasching, {Peter A} and Fortner, {Ren{\'e}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 T} 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 A G} 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 Onland-Moret, {N Charlotte} 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 Rodr{\'i}guez-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 Michal} 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",
note = "{\circledC}2018 American Association for Cancer Research.",
year = "2019",
month = "2",
day = "1",
doi = "10.1158/0008-5472.CAN-18-2726",
language = "English",
volume = "79",
pages = "505--517",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research (A A C R)",
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 - DeFazio, Anna

AU - Dennis, Joe

AU - Doherty, Jennifer A

AU - Dork, Thilo

AU - Eccles, Diana M

AU - Velez Edwards, Digna

AU - Fasching, Peter A

AU - Fortner, Renée 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 T

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 A G

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 - Onland-Moret, N Charlotte

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 - Rodríguez-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 Michal

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

N1 - ©2018 American Association for Cancer Research.

PY - 2019/2/1

Y1 - 2019/2/1

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 = 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.

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. 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.

UR - http://www.scopus.com/inward/record.url?scp=85060947651&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-18-2726

DO - 10.1158/0008-5472.CAN-18-2726

M3 - Journal article

VL - 79

SP - 505

EP - 517

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 3

ER -

ID: 56087148