Title: Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA
Authors: Earp, Madalene A ×
Kelemen, Linda E
Magliocco, Anthony M
Swenerton, Kenneth D
Chenevix-Trench, Georgia
Australian Cancer Study
Australian Ovarian Cancer Study Group
Lu, Yi
Hein, Alexander
Ekici, Arif B
Beckmann, Matthias W
Fasching, Peter A
Lambrechts, Diether
Despierre, Evelyn
Vergote, Ignace
Lambrechts, Sandrina
Doherty, Jennifer A
Rossing, Mary Anne
Chang-Claude, Jenny
Rudolph, Anja
Friel, Grace
Moysich, Kirsten B
Odunsi, Kunle
Sucheston-Campbell, Lara
Lurie, Galina
Goodman, Marc T
Carney, Michael E
Thompson, Pamela J
Runnebaum, Ingo B
Dürst, Matthias
Hillemanns, Peter
Dörk, Thilo
Antonenkova, Natalia
Bogdanova, Natalia
Leminen, Arto
Nevanlinna, Heli
Pelttari, Liisa M
Butzow, Ralf
Bunker, Clareann H
Modugno, Francesmary
Edwards, Robert P
Ness, Roberta B
du Bois, Andreas
Heitz, Florian
Schwaab, Ira
Harter, Philipp
Karlan, Beth Y
Walsh, Christine
Lester, Jenny
Jensen, Allan
Kjær, Susanne K
Høgdall, Claus K
Høgdall, Estrid
Lundvall, Lene
Sellers, Thomas A
Fridley, Brooke L
Goode, Ellen L
Cunningham, Julie M
Vierkant, Robert A
Giles, Graham G
Baglietto, Laura
Severi, Gianluca
Southey, Melissa C
Liang, Dong
Wu, Xifeng
Lu, Karen
Hildebrandt, Michelle A T
Levine, Douglas A
Bisogna, Maria
Schildkraut, Joellen M
Iversen, Edwin S
Weber, Rachel Palmieri
Berchuck, Andrew
Cramer, Daniel W
Terry, Kathryn L
Poole, Elizabeth M
Tworoger, Shelley S
Bandera, Elisa V
Chandran, Urmila
Orlow, Irene
Olson, Sara H
Wik, Elisabeth
Salvesen, Helga B
Bjorge, Line
Halle, Mari K
van Altena, Anne M
Aben, Katja K H
Kiemeney, Lambertus A
Massuger, Leon F A G
Pejovic, Tanja
Bean, Yukie T
Cybulski, Cezary
Gronwald, Jacek
Lubinski, Jan
Wentzensen, Nicolas
Brinton, Louise A
Lissowska, Jolanta
Garcia-Closas, Montserrat
Dicks, Ed
Dennis, Joe
Easton, Douglas F
Song, Honglin
Tyrer, Jonathan P
Pharoah, Paul D P
Eccles, Diana
Campbell, Ian G
Whittemore, Alice S
McGuire, Valerie
Sieh, Weiva
Rothstein, Joseph H
Flanagan, James M
Paul, James
Brown, Robert
Phelan, Catherine M
Risch, Harvey A
McLaughlin, John R
Narod, Steven A
Ziogas, Argyrios
Anton-Culver, Hoda
Gentry-Maharaj, Aleksandra
Menon, Usha
Gayther, Simon A
Ramus, Susan J
Wu, Anna H
Pearce, Celeste L
Pike, Malcolm C
Dansonka-Mieszkowska, Agnieszka
Rzepecka, Iwona K
Szafron, Lukasz M
Kupryjanczyk, Jolanta
Cook, Linda S
Le, Nhu D
Brooks-Wilson, Angela
On behalf of the Ovarian Cancer Association Consortium #
Issue Date: May-2014
Publisher: Springer-Verlag
Series Title: Human Genetics vol:133 issue:5 pages:481-97
Abstract: Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.
ISSN: 0340-6717
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gynaecological Oncology
× corresponding author
# (joint) last author

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