GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

Paul D P Pharoah; Ya Yu Tsai; Susan J. Ramus; Catherine M. Phelan; Ellen L. Goode; Kate Lawrenson; Melissa Buckley; Brooke L. Fridley; Jonathan P. Tyrer; Howard Shen; Rachel Weber; Rod Karevan; Melissa C. Larson; Honglin Song; Daniel C. Tessier; François Bacot; Daniel Vincent; Julie M. Cunningham; Joe Dennis; Ed Dicks; Katja K. Aben; Hoda Anton-Culver; Natalia Antonenkova; Sebastian M. Armasu; Laura Baglietto; Elisa V. Bandera; Matthias W. Beckmann; Michael J. Birrer; Greg Bloom; Natalia Bogdanova; James D. Brenton; Louise A. Brinton; Angela Brooks-Wilson; Robert Brown; Ralf Butzow; Ian Campbell; Michael E. Carney; Renato S. Carvalho; Jenny Chang-Claude; Y. Anne Chen; Zhihua Chen; Wong Ho Chow; Mine S. Cicek; Gerhard Coetzee; Linda S. Cook; Daniel W. Cramer; Cezary Cybulski; Agnieszka Dansonka-Mieszkowska; Evelyn Despierre; Jennifer A. Doherty; Thilo Dörk; Andreas Du Bois; Matthias Dürst; Diana Eccles; Robert Edwards; Arif B. Ekici; Peter A. Fasching; David Fenstermacher; James Flanagan; Yu Tang Gao; Montserrat Garcia-Closas; Aleksandra Gentry-Maharaj; Graham Giles; Anxhela Gjyshi; Martin Gore; Jacek Gronwald; Qi Guo; Mari K. Halle; Philipp Harter; Alexander Hein; Florian Heitz; Peter Hillemanns; Maureen Hoatlin; Estrid Høgdall; Claus K. Høgdall; Satoyo Hosono; Anna Jakubowska; Allan Jensen; Kimberly R. Kalli; Beth Y. Karlan; Linda E. Kelemen; Lambertus A. Kiemeney; Susanne Krüger Kjaer; Gottfried E. Konecny; Camilla Krakstad; Jolanta Kupryjanczyk; Diether Lambrechts; Sandrina Lambrechts; Nhu D. Le; Nathan Lee; Janet Lee; Arto Leminen; Boon Kiong Lim; Jolanta Lissowska; Jan Lubiński; Lene Lundvall; Galina Lurie; Leon F A G Massuger; Keitaro Matsuo; Valerie McGuire; John R. McLaughlin; Usha Menon; Francesmary Modugno; Kirsten B. Moysich; Toru Nakanishi; Steven A. Narod; Roberta B. Ness; Heli Nevanlinna; Stefan Nickels; Houtan Noushmehr; Kunle Odunsi; Sara Olson; Irene Orlow; James Paul; Tanja Pejovic; Liisa M. Pelttari; Jenny Permuth-Wey; Malcolm C. Pike; Elizabeth M. Poole; Xiaotao Qu; Harvey A. Risch; Lorna Rodriguez-Rodriguez; Mary Anne Rossing; Anja Rudolph; Ingo Runnebaum; Iwona K. Rzepecka; Helga B. Salvesen; Ira Schwaab; Gianluca Severi; Hui Shen; Vijayalakshmi Shridhar; Xiao Ou Shu; Weiva Sieh; Melissa C. Southey; Paul Spellman; Kazuo Tajima; Soo Hwang Teo; Kathryn L. Terry; Pamela J. Thompson; Agnieszka Timorek; Shelley S. Tworoger; Anne M. Van Altena; David Van Den Berg; Ignace Vergote; Robert A. Vierkant; Allison F. Vitonis; Shan Wang-Gohrke; Nicolas Wentzensen; Alice S. Whittemore; Elisabeth Wik; Boris Winterhoff; Yin Ling Woo; Anna H. Wu; Hannah P. Yang; Wei Zheng; Argyrios Ziogas; Famida Zulkifli; Marc T. Goodman; Per Hall; Douglas F. Easton; Celeste L. Pearce; Andrew Berchuck; Georgia Chenevix-Trench; Edwin Iversen; Alvaro N A Monteiro; Simon A. Gayther; Joellen M. Schildkraut; Thomas A. Sellers

doi:10.1038/ng.2564

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

Paul D P Pharoah, Ya Yu Tsai, Susan J. Ramus, Catherine M. Phelan, Ellen L. Goode, Kate Lawrenson, Melissa Buckley, Brooke L. Fridley, Jonathan P. Tyrer, Howard Shen, Rachel Weber, Rod Karevan, Melissa C. Larson, Honglin Song, Daniel C. Tessier, François Bacot, Daniel Vincent, Julie M. Cunningham, Joe Dennis, Ed DicksKatja K. Aben, Hoda Anton-Culver, Natalia Antonenkova, Sebastian M. Armasu, Laura Baglietto, Elisa V. Bandera, Matthias W. Beckmann, Michael J. Birrer, Greg Bloom, Natalia Bogdanova, James D. Brenton, Louise A. Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Butzow, Ian Campbell, Michael E. Carney, Renato S. Carvalho, Jenny Chang-Claude, Y. Anne Chen, Zhihua Chen, Wong Ho Chow, Mine S. Cicek, Gerhard Coetzee, Linda S. Cook, Daniel W. Cramer, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer A. Doherty, Thilo Dörk, Andreas Du Bois, Matthias Dürst, Diana Eccles, Robert Edwards, Arif B. Ekici, Peter A. Fasching, David Fenstermacher, James Flanagan, Yu Tang Gao, Montserrat Garcia-Closas, Aleksandra Gentry-Maharaj, Graham Giles, Anxhela Gjyshi, Martin Gore, Jacek Gronwald, Qi Guo, Mari K. Halle, Philipp Harter, Alexander Hein, Florian Heitz, Peter Hillemanns, Maureen Hoatlin, Estrid Høgdall, Claus K. Høgdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Kimberly R. Kalli, Beth Y. Karlan, Linda E. Kelemen, Lambertus A. Kiemeney, Susanne Krüger Kjaer, Gottfried E. Konecny, Camilla Krakstad, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu D. Le, Nathan Lee, Janet Lee, Arto Leminen, Boon Kiong Lim, Jolanta Lissowska, Jan Lubiński, Lene Lundvall, Galina Lurie, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R. McLaughlin, Usha Menon, Francesmary Modugno, Kirsten B. Moysich, Toru Nakanishi, Steven A. Narod, Roberta B. Ness, Heli Nevanlinna, Stefan Nickels, Houtan Noushmehr, Kunle Odunsi, Sara Olson, Irene Orlow, James Paul, Tanja Pejovic, Liisa M. Pelttari, Jenny Permuth-Wey, Malcolm C. Pike, Elizabeth M. Poole, Xiaotao Qu, Harvey A. Risch, Lorna Rodriguez-Rodriguez, Mary Anne Rossing, Anja Rudolph, Ingo Runnebaum, Iwona K. Rzepecka, Helga B. Salvesen, Ira Schwaab, Gianluca Severi, Hui Shen, Vijayalakshmi Shridhar, Xiao Ou Shu, Weiva Sieh, Melissa C. Southey, Paul Spellman, Kazuo Tajima, Soo Hwang Teo, Kathryn L. Terry, Pamela J. Thompson, Agnieszka Timorek, Shelley S. Tworoger, Anne M. Van Altena, David Van Den Berg, Ignace Vergote, Robert A. Vierkant, Allison F. Vitonis, Shan Wang-Gohrke, Nicolas Wentzensen, Alice S. Whittemore, Elisabeth Wik, Boris Winterhoff, Yin Ling Woo, Anna H. Wu, Hannah P. Yang, Wei Zheng, Argyrios Ziogas, Famida Zulkifli, Marc T. Goodman, Per Hall, Douglas F. Easton, Celeste L. Pearce, Andrew Berchuck, Georgia Chenevix-Trench, Edwin Iversen, Alvaro N A Monteiro, Simon A. Gayther, Joellen M. Schildkraut, Thomas A. Sellers

Obstetrics, Gynecology and Women's Health - Oncology

Research output: Contribution to journal › Article › peer-review

308 Scopus citations

Abstract

Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10^-9) and 10p12 (rs1243180, P = 1.8 × 10^-8) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10^-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.

Original language	English (US)
Pages (from-to)	362-370
Number of pages	9
Journal	Nature Genetics
Volume	45
Issue number	4
DOIs	https://doi.org/10.1038/ng.2564
State	Published - Apr 2013

Bibliographical note

Funding Information:
We thank all the individuals who took part in this study and all the researchers, clinicians and technical and administrative staff who made possible the many studies contributing to this work (a full list is provided in the Supplementary Note). The COGS project is funded through a European Commission’s Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were supported in part by the Genetic Associations and Mechanisms in Oncology (GAME-ON) and a National Cancer Institute Cancer Post-GWAS Initiative (U19-CA148112). Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium; funding for the project was provided by the Wellcome Trust under award 076113. A full list of the investigators who contributed to the generation of the data is available from the website (see URLs). The results published here are based in part on data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute; information about The Cancer Genome Atlas (TCGA) and the investigators and institutions who constitute the TCGA research network can be found on the website (see URLs).

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10.1038/ng.2564

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Pharoah, P. D. P., Tsai, Y. Y., Ramus, S. J., Phelan, C. M., Goode, E. L., Lawrenson, K., Buckley, M., Fridley, B. L., Tyrer, J. P., Shen, H., Weber, R., Karevan, R., Larson, M. C., Song, H., Tessier, D. C., Bacot, F., Vincent, D., Cunningham, J. M., Dennis, J., ... Sellers, T. A. (2013). GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nature Genetics, 45(4), 362-370. https://doi.org/10.1038/ng.2564

Pharoah, PDP, Tsai, YY, Ramus, SJ, Phelan, CM, Goode, EL, Lawrenson, K, Buckley, M, Fridley, BL, Tyrer, JP, Shen, H, Weber, R, Karevan, R, Larson, MC, Song, H, Tessier, DC, Bacot, F, Vincent, D, Cunningham, JM, Dennis, J, Dicks, E, Aben, KK, Anton-Culver, H, Antonenkova, N, Armasu, SM, Baglietto, L, Bandera, EV, Beckmann, MW, Birrer, MJ, Bloom, G, Bogdanova, N, Brenton, JD, Brinton, LA, Brooks-Wilson, A, Brown, R, Butzow, R, Campbell, I, Carney, ME, Carvalho, RS, Chang-Claude, J, Chen, YA, Chen, Z, Chow, WH, Cicek, MS, Coetzee, G, Cook, LS, Cramer, DW, Cybulski, C, Dansonka-Mieszkowska, A, Despierre, E, Doherty, JA, Dörk, T, Du Bois, A, Dürst, M, Eccles, D, Edwards, R, Ekici, AB, Fasching, PA, Fenstermacher, D, Flanagan, J, Gao, YT, Garcia-Closas, M, Gentry-Maharaj, A, Giles, G, Gjyshi, A, Gore, M, Gronwald, J, Guo, Q, Halle, MK, Harter, P, Hein, A, Heitz, F, Hillemanns, P, Hoatlin, M, Høgdall, E, Høgdall, CK, Hosono, S, Jakubowska, A, Jensen, A, Kalli, KR, Karlan, BY, Kelemen, LE, Kiemeney, LA, Kjaer, SK, Konecny, GE, Krakstad, C, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, ND, Lee, N, Lee, J, Leminen, A, Lim, BK, Lissowska, J, Lubiński, J, Lundvall, L, Lurie, G, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, Menon, U, Modugno, F, Moysich, KB, Nakanishi, T, Narod, SA, Ness, RB, Nevanlinna, H, Nickels, S, Noushmehr, H, Odunsi, K, Olson, S, Orlow, I, Paul, J, Pejovic, T, Pelttari, LM, Permuth-Wey, J, Pike, MC, Poole, EM, Qu, X, Risch, HA, Rodriguez-Rodriguez, L, Rossing, MA, Rudolph, A, Runnebaum, I, Rzepecka, IK, Salvesen, HB, Schwaab, I, Severi, G, Shen, H, Shridhar, V, Shu, XO, Sieh, W, Southey, MC, Spellman, P, Tajima, K, Teo, SH, Terry, KL, Thompson, PJ, Timorek, A, Tworoger, SS, Van Altena, AM, Van Den Berg, D, Vergote, I, Vierkant, RA, Vitonis, AF, Wang-Gohrke, S, Wentzensen, N, Whittemore, AS, Wik, E, Winterhoff, B, Woo, YL, Wu, AH, Yang, HP, Zheng, W, Ziogas, A, Zulkifli, F, Goodman, MT, Hall, P, Easton, DF, Pearce, CL, Berchuck, A, Chenevix-Trench, G, Iversen, E, Monteiro, ANA, Gayther, SA, Schildkraut, JM & Sellers, TA 2013, 'GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer', Nature Genetics, vol. 45, no. 4, pp. 362-370. https://doi.org/10.1038/ng.2564

@article{0f9fab67c714478c9b0b5d9131751d6e,

title = "GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer",

abstract = "Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10-9) and 10p12 (rs1243180, P = 1.8 × 10-8) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.",

author = "Pharoah, {Paul D P} and Tsai, {Ya Yu} and Ramus, {Susan J.} and Phelan, {Catherine M.} and Goode, {Ellen L.} and Kate Lawrenson and Melissa Buckley and Fridley, {Brooke L.} and Tyrer, {Jonathan P.} and Howard Shen and Rachel Weber and Rod Karevan and Larson, {Melissa C.} and Honglin Song and Tessier, {Daniel C.} and Fran{\c c}ois Bacot and Daniel Vincent and Cunningham, {Julie M.} and Joe Dennis and Ed Dicks and Aben, {Katja K.} and Hoda Anton-Culver and Natalia Antonenkova and Armasu, {Sebastian M.} and Laura Baglietto and Bandera, {Elisa V.} and Beckmann, {Matthias W.} and Birrer, {Michael J.} and Greg Bloom and Natalia Bogdanova and Brenton, {James D.} and Brinton, {Louise A.} and Angela Brooks-Wilson and Robert Brown and Ralf Butzow and Ian Campbell and Carney, {Michael E.} and Carvalho, {Renato S.} and Jenny Chang-Claude and Chen, {Y. Anne} and Zhihua Chen and Chow, {Wong Ho} and Cicek, {Mine S.} and Gerhard Coetzee and Cook, {Linda S.} and Cramer, {Daniel W.} and Cezary Cybulski and Agnieszka Dansonka-Mieszkowska and Evelyn Despierre and Doherty, {Jennifer A.} and Thilo D{\"o}rk and {Du Bois}, Andreas and Matthias D{\"u}rst and Diana Eccles and Robert Edwards and Ekici, {Arif B.} and Fasching, {Peter A.} and David Fenstermacher and James Flanagan and Gao, {Yu Tang} and Montserrat Garcia-Closas and Aleksandra Gentry-Maharaj and Graham Giles and Anxhela Gjyshi and Martin Gore and Jacek Gronwald and Qi Guo and Halle, {Mari K.} and Philipp Harter and Alexander Hein and Florian Heitz and Peter Hillemanns and Maureen Hoatlin and Estrid H{\o}gdall and H{\o}gdall, {Claus K.} and Satoyo Hosono and Anna Jakubowska and Allan Jensen and Kalli, {Kimberly R.} and Karlan, {Beth Y.} and Kelemen, {Linda E.} and Kiemeney, {Lambertus A.} and Kjaer, {Susanne Kr{\"u}ger} and Konecny, {Gottfried E.} and Camilla Krakstad and Jolanta Kupryjanczyk and Diether Lambrechts and Sandrina Lambrechts and Le, {Nhu D.} and Nathan Lee and Janet Lee and Arto Leminen and Lim, {Boon Kiong} and Jolanta Lissowska and Jan Lubi{\'n}ski and Lene Lundvall and Galina Lurie and Massuger, {Leon F A G} and Keitaro Matsuo and Valerie McGuire and McLaughlin, {John R.} and Usha Menon and Francesmary Modugno and Moysich, {Kirsten B.} and Toru Nakanishi and Narod, {Steven A.} and Ness, {Roberta B.} and Heli Nevanlinna and Stefan Nickels and Houtan Noushmehr and Kunle Odunsi and Sara Olson and Irene Orlow and James Paul and Tanja Pejovic and Pelttari, {Liisa M.} and Jenny Permuth-Wey and Pike, {Malcolm C.} and Poole, {Elizabeth M.} and Xiaotao Qu and Risch, {Harvey A.} and Lorna Rodriguez-Rodriguez and Rossing, {Mary Anne} and Anja Rudolph and Ingo Runnebaum and Rzepecka, {Iwona K.} and Salvesen, {Helga B.} and Ira Schwaab and Gianluca Severi and Hui Shen and Vijayalakshmi Shridhar and Shu, {Xiao Ou} and Weiva Sieh and Southey, {Melissa C.} and Paul Spellman and Kazuo Tajima and Teo, {Soo Hwang} and Terry, {Kathryn L.} and Thompson, {Pamela J.} and Agnieszka Timorek and Tworoger, {Shelley S.} and {Van Altena}, {Anne M.} and {Van Den Berg}, David and Ignace Vergote and Vierkant, {Robert A.} and Vitonis, {Allison F.} and Shan Wang-Gohrke and Nicolas Wentzensen and Whittemore, {Alice S.} and Elisabeth Wik and Boris Winterhoff and Woo, {Yin Ling} and Wu, {Anna H.} and Yang, {Hannah P.} and Wei Zheng and Argyrios Ziogas and Famida Zulkifli and Goodman, {Marc T.} and Per Hall and Easton, {Douglas F.} and Pearce, {Celeste L.} and Andrew Berchuck and Georgia Chenevix-Trench and Edwin Iversen and Monteiro, {Alvaro N A} and Gayther, {Simon A.} and Schildkraut, {Joellen M.} and Sellers, {Thomas A.}",

note = "Funding Information: We thank all the individuals who took part in this study and all the researchers, clinicians and technical and administrative staff who made possible the many studies contributing to this work (a full list is provided in the Supplementary Note). The COGS project is funded through a European Commission{\textquoteright}s Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were supported in part by the Genetic Associations and Mechanisms in Oncology (GAME-ON) and a National Cancer Institute Cancer Post-GWAS Initiative (U19-CA148112). Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium; funding for the project was provided by the Wellcome Trust under award 076113. A full list of the investigators who contributed to the generation of the data is available from the website (see URLs). The results published here are based in part on data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute; information about The Cancer Genome Atlas (TCGA) and the investigators and institutions who constitute the TCGA research network can be found on the website (see URLs).",

year = "2013",

month = apr,

doi = "10.1038/ng.2564",

language = "English (US)",

volume = "45",

pages = "362--370",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "4",

}

TY - JOUR

T1 - GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

AU - Pharoah, Paul D P

AU - Tsai, Ya Yu

AU - Ramus, Susan J.

AU - Phelan, Catherine M.

AU - Goode, Ellen L.

AU - Lawrenson, Kate

AU - Buckley, Melissa

AU - Fridley, Brooke L.

AU - Tyrer, Jonathan P.

AU - Shen, Howard

AU - Weber, Rachel

AU - Karevan, Rod

AU - Larson, Melissa C.

AU - Song, Honglin

AU - Tessier, Daniel C.

AU - Bacot, François

AU - Vincent, Daniel

AU - Cunningham, Julie M.

AU - Dennis, Joe

AU - Dicks, Ed

AU - Aben, Katja K.

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia

AU - Armasu, Sebastian M.

AU - Baglietto, Laura

AU - Bandera, Elisa V.

AU - Beckmann, Matthias W.

AU - Birrer, Michael J.

AU - Bloom, Greg

AU - Bogdanova, Natalia

AU - Brenton, James D.

AU - Brinton, Louise A.

AU - Brooks-Wilson, Angela

AU - Brown, Robert

AU - Butzow, Ralf

AU - Campbell, Ian

AU - Carney, Michael E.

AU - Carvalho, Renato S.

AU - Chang-Claude, Jenny

AU - Chen, Y. Anne

AU - Chen, Zhihua

AU - Chow, Wong Ho

AU - Cicek, Mine S.

AU - Coetzee, Gerhard

AU - Cook, Linda S.

AU - Cramer, Daniel W.

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 - Eccles, Diana

AU - Edwards, Robert

AU - Ekici, Arif B.

AU - Fasching, Peter A.

AU - Fenstermacher, David

AU - Flanagan, James

AU - Gao, Yu Tang

AU - Garcia-Closas, Montserrat

AU - Gentry-Maharaj, Aleksandra

AU - Giles, Graham

AU - Gjyshi, Anxhela

AU - Gore, Martin

AU - Gronwald, Jacek

AU - Guo, Qi

AU - Halle, Mari K.

AU - Harter, Philipp

AU - Hein, Alexander

AU - Heitz, Florian

AU - Hillemanns, Peter

AU - Hoatlin, Maureen

AU - Høgdall, Estrid

AU - Høgdall, Claus K.

AU - Hosono, Satoyo

AU - Jakubowska, Anna

AU - Jensen, Allan

AU - Kalli, Kimberly R.

AU - Karlan, Beth Y.

AU - Kelemen, Linda E.

AU - Kiemeney, Lambertus A.

AU - Kjaer, Susanne Krüger

AU - Konecny, Gottfried E.

AU - Krakstad, Camilla

AU - Kupryjanczyk, Jolanta

AU - Lambrechts, Diether

AU - Lambrechts, Sandrina

AU - Le, Nhu D.

AU - Lee, Nathan

AU - Lee, Janet

AU - Leminen, Arto

AU - Lim, Boon Kiong

AU - Lissowska, Jolanta

AU - Lubiński, Jan

AU - Lundvall, Lene

AU - Lurie, Galina

AU - Massuger, Leon F A G

AU - Matsuo, Keitaro

AU - McGuire, Valerie

AU - McLaughlin, John R.

AU - Menon, Usha

AU - Modugno, Francesmary

AU - Moysich, Kirsten B.

AU - Nakanishi, Toru

AU - Narod, Steven A.

AU - Ness, Roberta B.

AU - Nevanlinna, Heli

AU - Nickels, Stefan

AU - Noushmehr, Houtan

AU - Odunsi, Kunle

AU - Olson, Sara

AU - Orlow, Irene

AU - Paul, James

AU - Pejovic, Tanja

AU - Pelttari, Liisa M.

AU - Permuth-Wey, Jenny

AU - Pike, Malcolm C.

AU - Poole, Elizabeth M.

AU - Qu, Xiaotao

AU - Risch, Harvey A.

AU - Rodriguez-Rodriguez, Lorna

AU - Rossing, Mary Anne

AU - Rudolph, Anja

AU - Runnebaum, Ingo

AU - Rzepecka, Iwona K.

AU - Salvesen, Helga B.

AU - Schwaab, Ira

AU - Severi, Gianluca

AU - Shen, Hui

AU - Shridhar, Vijayalakshmi

AU - Shu, Xiao Ou

AU - Sieh, Weiva

AU - Southey, Melissa C.

AU - Spellman, Paul

AU - Tajima, Kazuo

AU - Teo, Soo Hwang

AU - Terry, Kathryn L.

AU - Thompson, Pamela J.

AU - Timorek, Agnieszka

AU - Tworoger, Shelley S.

AU - Van Altena, Anne M.

AU - Van Den Berg, David

AU - Vergote, Ignace

AU - Vierkant, Robert A.

AU - Vitonis, Allison F.

AU - Wang-Gohrke, Shan

AU - Wentzensen, Nicolas

AU - Whittemore, Alice S.

AU - Wik, Elisabeth

AU - Winterhoff, Boris

AU - Woo, Yin Ling

AU - Wu, Anna H.

AU - Yang, Hannah P.

AU - Zheng, Wei

AU - Ziogas, Argyrios

AU - Zulkifli, Famida

AU - Goodman, Marc T.

AU - Hall, Per

AU - Easton, Douglas F.

AU - Pearce, Celeste L.

AU - Berchuck, Andrew

AU - Chenevix-Trench, Georgia

AU - Iversen, Edwin

AU - Monteiro, Alvaro N A

AU - Gayther, Simon A.

AU - Schildkraut, Joellen M.

AU - Sellers, Thomas A.

N1 - Funding Information: We thank all the individuals who took part in this study and all the researchers, clinicians and technical and administrative staff who made possible the many studies contributing to this work (a full list is provided in the Supplementary Note). The COGS project is funded through a European Commission’s Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were supported in part by the Genetic Associations and Mechanisms in Oncology (GAME-ON) and a National Cancer Institute Cancer Post-GWAS Initiative (U19-CA148112). Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium; funding for the project was provided by the Wellcome Trust under award 076113. A full list of the investigators who contributed to the generation of the data is available from the website (see URLs). The results published here are based in part on data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute; information about The Cancer Genome Atlas (TCGA) and the investigators and institutions who constitute the TCGA research network can be found on the website (see URLs).

PY - 2013/4

Y1 - 2013/4

N2 - Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10-9) and 10p12 (rs1243180, P = 1.8 × 10-8) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.

AB - Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10-9) and 10p12 (rs1243180, P = 1.8 × 10-8) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.

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U2 - 10.1038/ng.2564

DO - 10.1038/ng.2564

M3 - Article

C2 - 23535730

AN - SCOPUS:84875707717

SN - 1061-4036

VL - 45

SP - 362

EP - 370

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

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