TY  - JOUR
AU  - Earp, Madalene
AU  - Tyrer, Jonathan P
AU  - Winham, Stacey J
AU  - Lin, Hui-Yi
AU  - Chornokur, Ganna
AU  - Dennis, Joe
AU  - Aben, Katja K H
AU  - Anton-Culver, Hoda
AU  - Antonenkova, Natalia
AU  - Bandera, Elisa V
AU  - Bean, Yukie T
AU  - Beckmann, Matthias W
AU  - Bjorge, Line
AU  - Bogdanova, Natalia
AU  - Brinton, Louise A
AU  - Brooks-Wilson, Angela
AU  - Bruinsma, Fiona
AU  - Bunker, Clareann H
AU  - Butzow, Ralf
AU  - Campbell, Ian G
AU  - Carty, Karen
AU  - Chang-Claude, Jenny
AU  - Cook, Linda S
AU  - Cramer, Daniel W
AU  - Cunningham, Julie M
AU  - Cybulski, Cezary
AU  - Dansonka-Mieszkowska, Agnieszka
AU  - Despierre, Evelyn
AU  - Doherty, Jennifer A
AU  - Dörk, Thilo
AU  - du Bois, Andreas
AU  - Dürst, Matthias
AU  - Easton, Douglas F
AU  - Eccles, Diana M
AU  - Edwards, Robert P
AU  - Ekici, Arif B
AU  - Fasching, Peter A
AU  - Fridley, Brooke L
AU  - Gentry-Maharaj, Aleksandra
AU  - Giles, Graham G
AU  - Glasspool, Rosalind
AU  - Goodman, Marc T
AU  - Gronwald, Jacek
AU  - Harter, Philipp
AU  - Hein, Alexander
AU  - Heitz, Florian
AU  - Hildebrandt, Michelle A T
AU  - Hillemanns, Peter
AU  - Hogdall, Claus K
AU  - Høgdall, Estrid
AU  - Hosono, Satoyo
AU  - Iversen, Edwin S
AU  - Jakubowska, Anna
AU  - Jensen, Allan
AU  - Ji, Bu-Tian
AU  - Jung, Audrey Ying-Chee
AU  - Karlan, Beth Y
AU  - Kellar, Melissa
AU  - Kiemeney, Lambertus A
AU  - Kiong Lim, Boon
AU  - Kjaer, Susanne K
AU  - Krakstad, Camilla
AU  - Kupryjanczyk, Jolanta
AU  - Lambrechts, Diether
AU  - Lambrechts, Sandrina
AU  - Le, Nhu D
AU  - Lele, Shashi
AU  - Lester, Jenny
AU  - Levine, Douglas A
AU  - Li, Zheng
AU  - Liang, Dong
AU  - Lissowska, Jolanta
AU  - Lu, Karen
AU  - Lubinski, Jan
AU  - Lundvall, Lene
AU  - Massuger, Leon F A G
AU  - Matsuo, Keitaro
AU  - McGuire, Valerie
AU  - McLaughlin, John R
AU  - McNeish, Iain
AU  - Menon, Usha
AU  - Milne, Roger L
AU  - Modugno, Francesmary
AU  - Moysich, Kirsten B
AU  - Ness, Roberta B
AU  - Nevanlinna, Heli
AU  - Odunsi, Kunle
AU  - Olson, Sara H
AU  - Orlow, Irene
AU  - Orsulic, Sandra
AU  - Paul, James
AU  - Pejovic, Tanja
AU  - Pelttari, Liisa M
AU  - Permuth, Jenny B
AU  - Pike, Malcolm C
AU  - Poole, Elizabeth M
AU  - Rosen, Barry
AU  - Rossing, Mary Anne
AU  - Rothstein, Joseph H
AU  - Runnebaum, Ingo B
AU  - Rzepecka, Iwona K
AU  - Schernhammer, Eva
AU  - Schwaab, Ira
AU  - Shu, Xiao-Ou
AU  - Shvetsov, Yurii B
AU  - Siddiqui, Nadeem
AU  - Sieh, Weiva
AU  - Song, Honglin
AU  - Southey, Melissa C
AU  - Spiewankiewicz, Beata
AU  - Sucheston-Campbell, Lara
AU  - Tangen, Ingvild L
AU  - Teo, Soo-Hwang
AU  - Terry, Kathryn L
AU  - Thompson, Pamela J
AU  - Thomsen, Lotte
AU  - Tworoger, Shelley S
AU  - van Altena, Anne M
AU  - Vergote, Ignace
AU  - Vestrheim Thomsen, Liv Cecilie
AU  - Vierkant, Robert A
AU  - Walsh, Christine S
AU  - Wang-Gohrke, Shan
AU  - Wentzensen, Nicolas
AU  - Whittemore, Alice S
AU  - Wicklund, Kristine G
AU  - Wilkens, Lynne R
AU  - Woo, Yin-Ling
AU  - Wu, Anna H
AU  - Wu, Xifeng
AU  - Xiang, Yong-Bing
AU  - Yang, Hannah
AU  - Zheng, Wei
AU  - Ziogas, Argyrios
AU  - Lee, Alice W
AU  - Pearce, Celeste L
AU  - Berchuck, Andrew
AU  - Schildkraut, Joellen M
AU  - Ramus, Susan J
AU  - Monteiro, Alvaro N A
AU  - Narod, Steven A
AU  - Sellers, Thomas A
AU  - Gayther, Simon A
AU  - Kelemen, Linda E
AU  - Chenevix-Trench, Georgia
AU  - Risch, Harvey A
AU  - Pharoah, Paul D P
AU  - Goode, Ellen L
AU  - Phelan, Catherine M
TI  - Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility.
JO  - PLoS one
VL  - 13
IS  - 7
SN  - 1932-6203
CY  - Lawrence, Kan.
PB  - PLoS
M1  - DKFZ-2018-01374
SP  - e0197561 -
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:29979793
C2  - pmc:PMC6034790
DO  - DOI:10.1371/journal.pone.0197561
UR  - https://inrepo02.dkfz.de/record/136945
ER  -