| Literature DB >> 30559148 |
Yaohua Yang1, Lang Wu1, Xiang Shu1, Yingchang Lu1, Xiao-Ou Shu1, Qiuyin Cai1, Alicia Beeghly-Fadiel1, Bingshan Li2, Fei Ye3, Andrew Berchuck4, Hoda Anton-Culver5, Susana Banerjee6, Javier Benitez7,8, Line Bjørge9,10, James D Brenton11, Ralf Butzow12, Ian G Campbell13,14, Jenny Chang-Claude15,16, Kexin Chen17, Linda S Cook18,19, Daniel W Cramer20,21, Anna deFazio22,23, Joe Dennis24, Jennifer A Doherty25, Thilo Dörk26, Diana M Eccles27, Digna Velez Edwards28, Peter A Fasching29,30, Renée T Fortner15, Simon A Gayther31, Graham G Giles32,33,34, Rosalind M Glasspool35, Ellen L Goode36, Marc T Goodman37, Jacek Gronwald38, Holly R Harris39,40, Florian Heitz41,42, Michelle A Hildebrandt43, Estrid Høgdall44,45, Claus K Høgdall46, David G Huntsman47,48,49,50, Siddhartha P Kar24, Beth Y Karlan51, Linda E Kelemen52, Lambertus A Kiemeney53, Susanne K Kjaer44,54, Anita Koushik55, Diether Lambrechts56, Nhu D Le57, Douglas A Levine58,59, Leon F Massuger60, Keitaro Matsuo61,62, Taymaa May63, Iain A McNeish64,65, Usha Menon66, Francesmary Modugno67,68, Alvaro N Monteiro69, Patricia G Moorman70, Kirsten B Moysich71, Roberta B Ness72, Heli Nevanlinna73, Håkan Olsson74, N Charlotte Onland-Moret75, Sue K Park76,77,78, James Paul35, Celeste L Pearce79,80, Tanja Pejovic81,82, Catherine M Phelan69, Malcolm C Pike80,83, Susan J Ramus84,85, Elio Riboli86, Cristina Rodriguez-Antona7,8, Isabelle Romieu87, Dale P Sandler88, Joellen M Schildkraut89, Veronica W Setiawan90, Kang Shan91, Nadeem Siddiqui92, Weiva Sieh93,94, Meir J Stampfer95, Rebecca Sutphen96, Anthony J Swerdlow97,98, Lukasz M Szafron99, Soo Hwang Teo100,101, Shelley S Tworoger69,102, Jonathan P Tyrer103, Penelope M Webb104, Nicolas Wentzensen105, Emily White106,40, Walter C Willett20,95,107, Alicja Wolk108,109, Yin Ling Woo110, Anna H Wu90, Li Yan111, Drakoulis Yannoukakos112, Georgia Chenevix-Trench113, Thomas A Sellers69, Paul D P Pharoah24,103, Wei Zheng1, Jirong Long114.
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. ©2018 American Association for Cancer Research.Entities:
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Year: 2018 PMID： 30559148 PMCID： PMC6359948 DOI： 10.1158/0008-5472.CAN-18-2726
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 13.312