BibTex format
@article{Earp:2018:10.1371/journal.pone.0197561,
author = {Earp, M and Tyrer, JP and Winham, SJ and Lin, H-Y and Chornokur, G and Dennis, J and Aben, KKH and Anton-Culver, H and Antonenkova, N and Bandera, EV and Bean, YT and Beckmann, MW and Bjorge, L and Bogdanova, N and Brinton, LA and Brooks-Wilson, A and Bruinsma, F and Bunker, CH and Butzow, R and Campbell, IG and Carty, K and Chang-Claude, J and Cook, LS and Cramer, DW and Cunningham, JM and Cybulski, C and Dansonka-Mieszkowska, A and Despierre, E and Doherty, JA and Dörk, T and du, Bois A and Dürst, M and Easton, DF and Eccles, DM and Edwards, RP and Ekici, AB and Fasching, PA and Fridley, BL and Gentry-Maharaj, A and Giles, GG and Glasspool, R and Goodman, MT and Gronwald, J and Harter, P and Hein, A and Heitz, F and Hildebrandt, MAT and Hillemanns, P and Hogdall, CK and Høgdall, E and Hosono, S and Iversen, ES and Jakubowska, A and Jensen, A and Ji, B-T and Jung, AY and Karlan, BY and Kellar, M and Kiemeney, LA and Kiong, Lim B and Kjaer, SK and Krakstad, C and Kupryjanczyk, J and La},
doi = {10.1371/journal.pone.0197561},
journal = {PLoS ONE},
pages = {1--13},
title = {Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility},
url = {http://dx.doi.org/10.1371/journal.pone.0197561},
volume = {13},
year = {2018}
}
RIS format (EndNote, RefMan)
TY - JOUR
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.
AU - Earp,M
AU - Tyrer,JP
AU - Winham,SJ
AU - Lin,H-Y
AU - Chornokur,G
AU - Dennis,J
AU - Aben,KKH
AU - Anton-Culver,H
AU - Antonenkova,N
AU - Bandera,EV
AU - Bean,YT
AU - Beckmann,MW
AU - Bjorge,L
AU - Bogdanova,N
AU - Brinton,LA
AU - Brooks-Wilson,A
AU - Bruinsma,F
AU - Bunker,CH
AU - Butzow,R
AU - Campbell,IG
AU - Carty,K
AU - Chang-Claude,J
AU - Cook,LS
AU - Cramer,DW
AU - Cunningham,JM
AU - Cybulski,C
AU - Dansonka-Mieszkowska,A
AU - Despierre,E
AU - Doherty,JA
AU - Dörk,T
AU - du,Bois A
AU - Dürst,M
AU - Easton,DF
AU - Eccles,DM
AU - Edwards,RP
AU - Ekici,AB
AU - Fasching,PA
AU - Fridley,BL
AU - Gentry-Maharaj,A
AU - Giles,GG
AU - Glasspool,R
AU - Goodman,MT
AU - Gronwald,J
AU - Harter,P
AU - Hein,A
AU - Heitz,F
AU - Hildebrandt,MAT
AU - Hillemanns,P
AU - Hogdall,CK
AU - Høgdall,E
AU - Hosono,S
AU - Iversen,ES
AU - Jakubowska,A
AU - Jensen,A
AU - Ji,B-T
AU - Jung,AY
AU - Karlan,BY
AU - Kellar,M
AU - Kiemeney,LA
AU - Kiong,Lim B
AU - Kjaer,SK
AU - Krakstad,C
AU - Kupryjanczyk,J
AU - Lambrechts,D
AU - Lambrechts,S
AU - Le,ND
AU - Lele,S
AU - Lester,J
AU - Levine,DA
AU - Li,Z
AU - Liang,D
AU - Lissowska,J
AU - Lu,K
AU - Lubinski,J
AU - Lundvall,L
AU - Massuger,LFAG
AU - Matsuo,K
AU - McGuire,V
AU - McLaughlin,JR
AU - McNeish,I
AU - Menon,U
AU - Milne,RL
AU - Modugno,F
AU - Moysich,KB
AU - Ness,RB
AU - Nevanlinna,H
AU - Odunsi,K
AU - Olson,SH
AU - Orlow,I
AU - Orsulic,S
AU - Paul,J
AU - Pejovic,T
AU - Pelttari,LM
AU - Permuth,JB
AU - Pike,MC
AU - Poole,EM
AU - Rosen,B
AU - Rossing,MA
AU - Rothstein,JH
AU - Runnebaum,IB
AU - Rzepecka,IK
AU - Schernhammer,E
AU - Schwaab,I
AU - Shu,X-O
AU - Shvetsov,YB
AU - Siddiqui,N
AU - Sieh,W
AU - Song,H
AU - Southey,MC
AU - Spiewankiewicz,B
AU - Sucheston-Campbell,L
AU - Tangen,IL
AU - Teo,S-H
AU - Terry,KL
AU - Thompson,PJ
AU - Thomsen,L
AU - Tworoger,SS
AU - van,Altena AM
AU - Vergote,I
AU - Vestrheim,Thomsen LC
AU - Vierkant,RA
AU - Walsh,CS
AU - Wang-Gohrke,S
AU - Wentzensen,N
AU - Whittemore,AS
AU - Wicklund,KG
AU - Wilkens,LR
AU - Woo,Y-L
AU - Wu,AH
AU - Wu,X
AU - Xiang,Y-B
AU - Yang,H
AU - Zheng,W
AU - Ziogas,A
AU - Lee,AW
AU - Pearce,CL
AU - Berchuck,A
AU - Schildkraut,JM
AU - Ramus,SJ
AU - Monteiro,ANA
AU - Narod,SA
AU - Sellers,TA
AU - Gayther,SA
AU - Kelemen,LE
AU - Chenevix-Trench,G
AU - Risch,HA
AU - Pharoah,PDP
AU - Goode,EL
AU - Phelan,CM
DO - 10.1371/journal.pone.0197561
EP - 13
PY - 2018///
SN - 1932-6203
SP - 1
TI - Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility
T2 - PLoS ONE
UR - http://dx.doi.org/10.1371/journal.pone.0197561
UR - https://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0197561
VL - 13
ER -