The University of Southampton
University of Southampton Institutional Repository

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31
Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31
Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3? untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene–environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10?8) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10?10). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.
1627
Permuth-Wey, Jennifer
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Lawrenson, Kate
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Shen, Howard C.
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Velkova, Aneliya
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Tyrer, Jonathan P.
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Chen, Zhihua
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Lin, Hui-Yi
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Ann Chen, Y.
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Tsai, Ya-Yu
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Qu, Xiaotao
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Ramus, Susan J.
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Karevan, Rod
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Lee, Janet
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Lee, Nathan
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Larson, Melissa C.
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Aben, Katja K.
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Anton-Culver, Hoda
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Antonenkova, Natalia
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Antoniou, Antonis C.
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Armasu, Sebastian M.
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Bacot, François
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Baglietto, Laura
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Bandera, Elisa V.
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Barnholtz-Sloan, Jill
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Beckmann, Matthias W.
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Birrer, Michael J.
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Bloom, Greg
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Bogdanova, Natalia
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Brinton, Louise A.
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Brooks-Wilson, Angela
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Brown, Robert
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Butzow, Ralf
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Cai, Qiuyin
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Campbell, Ian
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Chang-Claude, Jenny
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Chanock, Stephen
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Chenevix-Trench, Georgia
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Cheng, Jin Q.
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Cicek, Mine S.
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Coetzee, Gerhard A.
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Cook, Linda S.
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Couch, Fergus J.
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Cramer, Daniel W.
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Cunningham, Julie M.
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Dansonka-Mieszkowska, Agnieszka
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Despierre, Evelyn
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Doherty, Jennifer A.
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Dörk, Thilo
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du Bois, Andreas
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Dürst, Matthias
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Easton, Douglas F.
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Edwards, Robert
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Fenstermacher, David A.
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Flanagan, James M.
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Gonzalez-Bosquet, Jesus
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Goodman, Marc T.
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Gore, Martin
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Górski, Bohdan
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Hall, Per
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Hillemanns, Peter
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Hoatlin, Maureen
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Høgdall, Claus K.
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Høgdall, Estrid
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Hosono, Satoyo
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Jakubowska, Anna
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Jim, Heather
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Kalli, Kimberly R.
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Karlan, Beth Y.
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Kaye, Stanley B.
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Kelemen, Linda E.
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Kiemeney, Lambertus A.
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Kikkawa, Fumitaka
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Konecny, Gottfried E.
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Krakstad, Camilla
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McLaughlin, John R.
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Menon, Usha
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Nevanlinna, Heli
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Nickels, Stefan
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van Altena, Anne M.
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Brooks-Wilson, Angela
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Butzow, Ralf
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Chanock, Stephen
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du Bois, Andreas
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Eccles, Diana
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Heitz, Florian
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Hosono, Satoyo
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Lubiński, Jan
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Massuger, Leon F.A.G
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McLaughlin, John R.
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Modugno, Francesmary
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Moysich, Kirsten B.
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Nakanishi, Toru
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Nevanlinna, Heli
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Nickels, Stefan
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Noushmehr, Houtan
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Odunsi, Kunle
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Orlow, Irene
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Paul, James
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Pearce, Celeste L.
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Pejovic, Tanja
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Pelttari, Liisa M.
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Poole, Elizabeth M.
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Raska, Paola
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Renner, Stefan P.
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Risch, Harvey A.
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Rodriguez-Rodriguez, Lorna
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Anne Rossing, Mary
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Rudolph, Anja
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Runnebaum, Ingo B.
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Rzepecka, Iwona K.
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Salvesen, Helga B.
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Schwaab, Ira
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Severi, Gianluca
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Shridhar, Viji
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Shvetsov, Yurii B.
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Southey, Melissa C.
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Spiewankiewicz, Beata
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Stram, Daniel
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Sutphen, Rebecca
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Teo, Soo-Hwang
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Tworoger, Shelley S.
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van Altena, Anne M.
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Wentzensen, Nicolas
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Whittemore, Alice S.
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Winterhoff, Boris
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Zheng, Wei
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Ziogas, Argyrios
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Zulkifli, Famida
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Phelan, Catherine M.
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Iversen, Edwin
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Pharoah, Paul D.P.
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Monteiro, Alvaro N.A.
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Sellers, Thomas A.
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Gayther, Simon A.
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Permuth-Wey, Jennifer, Lawrenson, Kate, Shen, Howard C., Velkova, Aneliya, Tyrer, Jonathan P., Chen, Zhihua, Lin, Hui-Yi, Ann Chen, Y., Tsai, Ya-Yu, Qu, Xiaotao, Ramus, Susan J., Karevan, Rod, Lee, Janet, Lee, Nathan, Larson, Melissa C., Aben, Katja K., Anton-Culver, Hoda, Antonenkova, Natalia, Antoniou, Antonis C., Armasu, Sebastian M., Bacot, François, Baglietto, Laura, Bandera, Elisa V., Barnholtz-Sloan, Jill, Beckmann, Matthias W., Birrer, Michael J., Bloom, Greg, Bogdanova, Natalia, Brinton, Louise A., Brooks-Wilson, Angela, Brown, Robert, Butzow, Ralf, Cai, Qiuyin, Campbell, Ian, Chang-Claude, Jenny, Chanock, Stephen, Chenevix-Trench, Georgia, Cheng, Jin Q., Cicek, Mine S., Coetzee, Gerhard A., Cook, Linda S., Couch, Fergus J., Cramer, Daniel W., Cunningham, Julie M., Dansonka-Mieszkowska, Agnieszka, Despierre, Evelyn, Doherty, Jennifer A., Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Easton, Douglas F., Eccles, Diana, Edwards, Robert, Ekici, Arif B., Fasching, Peter A., Fenstermacher, David A., Flanagan, James M., Garcia-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Giles, Graham G., Glasspool, Rosalind M., Gonzalez-Bosquet, Jesus, Goodman, Marc T., Gore, Martin, Górski, Bohdan, Gronwald, Jacek, Hall, Per, Halle, Mari K., Harter, Philipp, Heitz, Florian, Hillemanns, Peter, Hoatlin, Maureen, Høgdall, Claus K., Høgdall, Estrid, Hosono, Satoyo, Jakubowska, Anna, Jensen, Allan, Jim, Heather, Kalli, Kimberly R., Karlan, Beth Y., Kaye, Stanley B., Kelemen, Linda E., Kiemeney, Lambertus A., Kikkawa, Fumitaka, Konecny, Gottfried E., Krakstad, Camilla, Krüger Kjaer, Susanne, Kupryjanczyk, Jolanta, Lambrechts, Diether, Lambrechts, Sandrina, Lancaster, Johnathan M., Le, Nhu D., Leminen, Arto, Levine, Douglas A., Liang, Dong, Kiong Lim, Boon, Lin, Jie, Lissowska, Jolanta, Lu, Karen H., Lubiński, Jan, Lurie, Galina, Massuger, Leon F.A.G, Matsuo, Keitaro, McGuire, Valerie, McLaughlin, John R., Menon, Usha, Modugno, Francesmary, Moysich, Kirsten B., Nakanishi, Toru, Narod, Steven A., Nedergaard, Lotte, Ness, Roberta B., Nevanlinna, Heli, Nickels, Stefan, Noushmehr, Houtan, Odunsi, Kunle, Olson, Sara H., Orlow, Irene, Paul, James, Pearce, Celeste L., Pejovic, Tanja, Pelttari, Liisa M., Pike, Malcolm C., Poole, Elizabeth M., Raska, Paola, Renner, Stefan P., Risch, Harvey A., Rodriguez-Rodriguez, Lorna, Anne Rossing, Mary, Rudolph, Anja, Runnebaum, Ingo B., Rzepecka, Iwona K., Salvesen, Helga B., Schwaab, Ira, Severi, Gianluca, Shridhar, Viji, Shu, Xiao-Ou, Shvetsov, Yurii B., Sieh, Weiva, Song, Honglin, Southey, Melissa C., Spiewankiewicz, Beata, Stram, Daniel, Sutphen, Rebecca, Teo, Soo-Hwang, Terry, Kathryn L., Tessier, Daniel C., Thompson, Pamela J., Tworoger, Shelley S., van Altena, Anne M., Vergote, Ignace, Vierkant, Robert A., Vincent, Daniel, Vitonis, Allison F., Wang-Gohrke, Shan, Palmieri Weber, Rachel, Wentzensen, Nicolas, Whittemore, Alice S., Wik, Elisabeth, Wilkens, Lynne R., Winterhoff, Boris, Ling Woo, Yin, Wu, Anna H., Xiang, Yong-Bing, Yang, Hannah P., Zheng, Wei, Ziogas, Argyrios, Zulkifli, Famida, Phelan, Catherine M., Iversen, Edwin, Schildkraut, Joellen M., Berchuck, Andrew, Fridley, Brooke L., Goode, Ellen L., Pharoah, Paul D.P., Monteiro, Alvaro N.A., Sellers, Thomas A. and Gayther, Simon A. (2013) Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31. Nature Communications, 4, 1627. (doi:10.1038/ncomms2613).

Record type: Article

Abstract

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3? untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA-related single-nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene–environment Study. We identify several miRSNPs associated with invasive serous EOC risk (odds ratio=1.12, P=10?8) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion (P=10?10). Variation at 17q21.31 is associated with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.

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Published date: 27 March 2013
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 352326
URI: http://eprints.soton.ac.uk/id/eprint/352326
PURE UUID: dc92185a-1247-4f7d-ac3c-941091eaea9c
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 14 May 2013 14:27
Last modified: 15 Mar 2024 02:40

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Contributors

Author: Jennifer Permuth-Wey
Author: Kate Lawrenson
Author: Howard C. Shen
Author: Aneliya Velkova
Author: Jonathan P. Tyrer
Author: Zhihua Chen
Author: Hui-Yi Lin
Author: Y. Ann Chen
Author: Ya-Yu Tsai
Author: Xiaotao Qu
Author: Susan J. Ramus
Author: Rod Karevan
Author: Janet Lee
Author: Nathan Lee
Author: Melissa C. Larson
Author: Katja K. Aben
Author: Hoda Anton-Culver
Author: Natalia Antonenkova
Author: Antonis C. Antoniou
Author: Sebastian M. Armasu
Author: François Bacot
Author: Laura Baglietto
Author: Elisa V. Bandera
Author: Jill Barnholtz-Sloan
Author: Matthias W. Beckmann
Author: Michael J. Birrer
Author: Greg Bloom
Author: Natalia Bogdanova
Author: Louise A. Brinton
Author: Angela Brooks-Wilson
Author: Robert Brown
Author: Ralf Butzow
Author: Qiuyin Cai
Author: Ian Campbell
Author: Jenny Chang-Claude
Author: Stephen Chanock
Author: Georgia Chenevix-Trench
Author: Jin Q. Cheng
Author: Mine S. Cicek
Author: Gerhard A. Coetzee
Author: Linda S. Cook
Author: Fergus J. Couch
Author: Daniel W. Cramer
Author: Julie M. Cunningham
Author: Agnieszka Dansonka-Mieszkowska
Author: Evelyn Despierre
Author: Jennifer A. Doherty
Author: Thilo Dörk
Author: Andreas du Bois
Author: Matthias Dürst
Author: Douglas F. Easton
Author: Diana Eccles ORCID iD
Author: Robert Edwards
Author: Arif B. Ekici
Author: Peter A. Fasching
Author: David A. Fenstermacher
Author: James M. Flanagan
Author: Montserrat Garcia-Closas
Author: Aleksandra Gentry-Maharaj
Author: Graham G. Giles
Author: Rosalind M. Glasspool
Author: Jesus Gonzalez-Bosquet
Author: Marc T. Goodman
Author: Martin Gore
Author: Bohdan Górski
Author: Jacek Gronwald
Author: Per Hall
Author: Mari K. Halle
Author: Philipp Harter
Author: Florian Heitz
Author: Peter Hillemanns
Author: Maureen Hoatlin
Author: Claus K. Høgdall
Author: Estrid Høgdall
Author: Satoyo Hosono
Author: Anna Jakubowska
Author: Allan Jensen
Author: Heather Jim
Author: Kimberly R. Kalli
Author: Beth Y. Karlan
Author: Stanley B. Kaye
Author: Linda E. Kelemen
Author: Lambertus A. Kiemeney
Author: Fumitaka Kikkawa
Author: Gottfried E. Konecny
Author: Camilla Krakstad
Author: Susanne Krüger Kjaer
Author: Jolanta Kupryjanczyk
Author: Diether Lambrechts
Author: Sandrina Lambrechts
Author: Johnathan M. Lancaster
Author: Nhu D. Le
Author: Arto Leminen
Author: Douglas A. Levine
Author: Dong Liang
Author: Boon Kiong Lim
Author: Jie Lin
Author: Jolanta Lissowska
Author: Karen H. Lu
Author: Jan Lubiński
Author: Galina Lurie
Author: Leon F.A.G Massuger
Author: Keitaro Matsuo
Author: Valerie McGuire
Author: John R. McLaughlin
Author: Usha Menon
Author: Francesmary Modugno
Author: Kirsten B. Moysich
Author: Toru Nakanishi
Author: Steven A. Narod
Author: Lotte Nedergaard
Author: Roberta B. Ness
Author: Heli Nevanlinna
Author: Stefan Nickels
Author: Houtan Noushmehr
Author: Kunle Odunsi
Author: Sara H. Olson
Author: Irene Orlow
Author: James Paul
Author: Celeste L. Pearce
Author: Tanja Pejovic
Author: Liisa M. Pelttari
Author: Malcolm C. Pike
Author: Elizabeth M. Poole
Author: Paola Raska
Author: Stefan P. Renner
Author: Harvey A. Risch
Author: Lorna Rodriguez-Rodriguez
Author: Mary Anne Rossing
Author: Anja Rudolph
Author: Ingo B. Runnebaum
Author: Iwona K. Rzepecka
Author: Helga B. Salvesen
Author: Ira Schwaab
Author: Gianluca Severi
Author: Viji Shridhar
Author: Xiao-Ou Shu
Author: Yurii B. Shvetsov
Author: Weiva Sieh
Author: Honglin Song
Author: Melissa C. Southey
Author: Beata Spiewankiewicz
Author: Daniel Stram
Author: Rebecca Sutphen
Author: Soo-Hwang Teo
Author: Kathryn L. Terry
Author: Daniel C. Tessier
Author: Pamela J. Thompson
Author: Shelley S. Tworoger
Author: Anne M. van Altena
Author: Ignace Vergote
Author: Robert A. Vierkant
Author: Daniel Vincent
Author: Allison F. Vitonis
Author: Shan Wang-Gohrke
Author: Rachel Palmieri Weber
Author: Nicolas Wentzensen
Author: Alice S. Whittemore
Author: Elisabeth Wik
Author: Lynne R. Wilkens
Author: Boris Winterhoff
Author: Yin Ling Woo
Author: Anna H. Wu
Author: Yong-Bing Xiang
Author: Hannah P. Yang
Author: Wei Zheng
Author: Argyrios Ziogas
Author: Famida Zulkifli
Author: Catherine M. Phelan
Author: Edwin Iversen
Author: Joellen M. Schildkraut
Author: Andrew Berchuck
Author: Brooke L. Fridley
Author: Ellen L. Goode
Author: Paul D.P. Pharoah
Author: Alvaro N.A. Monteiro
Author: Thomas A. Sellers
Author: Simon A. Gayther

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