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@ARTICLE{Yang:142948,
author = {Y. Yang and L. Wu and X. Shu and Y. Lu and X.-O. Shu and Q.
Cai and A. Beeghly-Fadiel and B. Li and F. Ye and A.
Berchuck and H. Anton-Culver and S. Banerjee and J. Benitez
and L. Bjørge and J. D. Brenton and R. Butzow and I. G.
Campbell and J. Chang-Claude$^*$ and K. Chen and L. S. Cook
and D. W. Cramer and A. deFazio and J. Dennis and J. A.
Doherty and T. Dörk and D. M. Eccles and D. V. Edwards and
P. A. Fasching and R. Turzanski-Fortner$^*$ and S. A.
Gayther and G. G. Giles and R. M. Glasspool and E. L. Goode
and M. T. Goodman and J. Gronwald and H. R. Harris and F.
Heitz and M. A. Hildebrandt and E. Høgdall and C. K.
Høgdall and D. G. Huntsman and S. P. Kar and B. Y. Karlan
and L. E. Kelemen and L. A. Kiemeney and S. K. Kjaer and A.
Koushik and D. Lambrechts and N. D. Le and D. A. Levine and
L. F. Massuger and K. Matsuo and T. May and I. A. McNeish
and U. Menon and F. Modugno and A. N. Monteiro and P. G.
Moorman and K. B. Moysich and R. B. Ness and H. Nevanlinna
and H. Olsson and N. C. Onland-Moret and S. K. Park and J.
Paul and C. L. Pearce and T. Pejovic and C. M. Phelan and M.
C. Pike and S. J. Ramus and E. Riboli and C.
Rodriguez-Antona and I. Romieu and D. P. Sandler and J. M.
Schildkraut and V. W. Setiawan and K. Shan and N. Siddiqui
and W. Sieh and M. J. Stampfer and R. Sutphen and A. J.
Swerdlow and L. M. Szafron and S. H. Teo and S. S. Tworoger
and J. P. Tyrer and P. M. Webb and N. Wentzensen and E.
White and W. C. Willett and A. Wolk and Y. L. Woo and A. H.
Wu and L. Yan and D. Yannoukakos and G. Chenevix-Trench and
T. A. Sellers and P. D. P. Pharoah and W. Zheng and J. Long},
title = {{G}enetic {D}ata from {N}early 63,000 {W}omen of {E}uropean
{D}escent {P}redicts {DNA} {M}ethylation {B}iomarkers and
{E}pithelial {O}varian {C}ancer {R}isk.},
journal = {Cancer research},
volume = {79},
number = {3},
issn = {1538-7445},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2019-00576},
pages = {505-517},
year = {2019},
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.},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30559148},
pmc = {pmc:PMC6359948},
doi = {10.1158/0008-5472.CAN-18-2726},
url = {https://inrepo02.dkfz.de/record/142948},
}