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@ARTICLE{Earp:136945,
author = {M. Earp and J. P. Tyrer and S. J. Winham and H.-Y. Lin and
G. Chornokur and J. Dennis and K. K. H. Aben and H.
Anton-Culver and N. Antonenkova and E. V. Bandera and Y. T.
Bean and M. W. Beckmann and L. Bjorge and N. Bogdanova and
L. A. Brinton and A. Brooks-Wilson and F. Bruinsma and C. H.
Bunker and R. Butzow and I. G. Campbell and K. Carty and J.
Chang-Claude$^*$ and L. S. Cook and D. W. Cramer and J. M.
Cunningham and C. Cybulski and A. Dansonka-Mieszkowska and
E. Despierre and J. A. Doherty and T. Dörk and A. du Bois
and M. Dürst and D. F. Easton and D. M. Eccles and R. P.
Edwards and A. B. Ekici and P. A. Fasching and B. L. Fridley
and A. Gentry-Maharaj and G. G. Giles and R. Glasspool and
M. T. Goodman and J. Gronwald and P. Harter and A. Hein and
F. Heitz and M. A. T. Hildebrandt and P. Hillemanns and C.
K. Hogdall and E. Høgdall and S. Hosono and E. S. Iversen
and A. Jakubowska and A. Jensen and B.-T. Ji and A. Y.
Jung$^*$ and B. Y. Karlan and M. Kellar and L. A. Kiemeney
and B. Kiong Lim and S. K. Kjaer and C. Krakstad and J.
Kupryjanczyk and D. Lambrechts and S. Lambrechts and N. D.
Le and S. Lele and J. Lester and D. A. Levine and Z. Li and
D. Liang and J. Lissowska and K. Lu and J. Lubinski and L.
Lundvall and L. F. A. G. Massuger and K. Matsuo and V.
McGuire and J. R. McLaughlin and I. McNeish and U. Menon and
R. L. Milne and F. Modugno and K. B. Moysich and R. B. Ness
and H. Nevanlinna and K. Odunsi and S. H. Olson and I. Orlow
and S. Orsulic and J. Paul and T. Pejovic and L. M. Pelttari
and J. B. Permuth and M. C. Pike and E. M. Poole and B.
Rosen and M. A. Rossing and J. H. Rothstein and I. B.
Runnebaum and I. K. Rzepecka and E. Schernhammer and I.
Schwaab and X.-O. Shu and Y. B. Shvetsov and N. Siddiqui and
W. Sieh and H. Song and M. C. Southey and B. Spiewankiewicz
and L. Sucheston-Campbell and I. L. Tangen and S.-H. Teo and
K. L. Terry and P. J. Thompson and L. Thomsen and S. S.
Tworoger and A. M. van Altena and I. Vergote and L. C.
Vestrheim Thomsen and R. A. Vierkant and C. S. Walsh and S.
Wang-Gohrke$^*$ and N. Wentzensen and A. S. Whittemore and
K. G. Wicklund and L. R. Wilkens and Y.-L. Woo and A. H. Wu
and X. Wu and Y.-B. Xiang and H. Yang and W. Zheng and A.
Ziogas and A. W. Lee and C. L. Pearce and A. Berchuck and J.
M. Schildkraut and S. J. Ramus and A. N. A. Monteiro and S.
A. Narod and T. A. Sellers and S. A. Gayther and L. E.
Kelemen and G. Chenevix-Trench and H. A. Risch and P. D. P.
Pharoah and E. L. Goode and C. M. Phelan},
title = {{V}ariants in genes encoding small {GTP}ases and
association with epithelial ovarian cancer susceptibility.},
journal = {PLoS one},
volume = {13},
number = {7},
issn = {1932-6203},
address = {Lawrence, Kan.},
publisher = {PLoS},
reportid = {DKFZ-2018-01374},
pages = {e0197561 -},
year = {2018},
abstract = {Epithelial ovarian cancer (EOC) is the fifth leading cause
of cancer mortality in American women. Normal ovarian
physiology is intricately connected to small GTP binding
proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and
Ran) which govern processes such as signal transduction,
cell proliferation, cell motility, and vesicle transport. We
hypothesized that common germline variation in genes
encoding small GTPases is associated with EOC risk. We
investigated 322 variants in 88 small GTPase genes in
germline DNA of 18,736 EOC patients and 26,138 controls of
European ancestry using a custom genotype array and logistic
regression fitting log-additive models. Functional
annotation was used to identify biofeatures and expression
quantitative trait loci that intersect with risk variants.
One variant, ARHGEF10L (Rho guanine nucleotide exchange
factor 10 like) rs2256787, was associated with increased
endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other
variants of interest included another in ARHGEF10L,
rs10788679, which was associated with invasive serous EOC
risk (OR = 1.07, p = 0.00026) and two variants in AKAP6
(A-kinase anchoring protein 6) which were associated with
risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033;
rs927062, OR = 0.94, p = 0.00059). Functional annotation
revealed that the two ARHGEF10L variants were located in
super-enhancer regions and that AKAP6 rs927062 was
associated with expression of GTPase gene ARHGAP5 (Rho
GTPase activating protein 5). Inherited variants in
ARHGEF10L and AKAP6, with potential transcriptional
regulatory function and association with EOC risk, warrant
investigation in independent EOC study populations.},
cin = {C020 / L101},
ddc = {500},
cid = {I:(DE-He78)C020-20160331 / I:(DE-He78)L101-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29979793},
pmc = {pmc:PMC6034790},
doi = {10.1371/journal.pone.0197561},
url = {https://inrepo02.dkfz.de/record/136945},
}