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

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

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Susan Ramus
Pharoah et al., 2013

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Nature Research, Nature Genetics, 4(45), p. 362-370, 2013

DOI: 10.1038/ng.2564

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@article{Pharoah2013,
  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 x 10(-9)) and 10p12 (rs1243180, P = 1.8 x 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 x 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. Pdp and Tsai, Ya-Yu and Ramus, Susan J. and Phelan, Catherine M. and Goode, Ellen L. and Lawrenson, Kate and Buckley, Melissa and Fridley, Brooke L. and Tyrer, Jonathan P. and Shen, Howard and Weber, Rachel and Karevan, Rod and Larson, Melissa C. and Song, Honglin and Tessier, Daniel C. and Bacot, François and Study, stralian Cancer and Vincent, Daniel and Cunningham, Julie M. and Group, stralian Ovarian Cancer Study and Dennis, Joe and Dicks, Ed and Aben, Katja K. H. and Anton-Culver, Hoda and Antonenkova, Natalia and Armasu, Sebastian M. and Baglietto, Laura and Bandera, Elisa V. and du Bois, Andreas and Australian Cancer, Study and Beckmann, Matthias W. and Birrer, Michael J. and Anne Chen, Y. and Bloom, Greg and Bogdanova, Natalia and Australian Ovarian Cancer Study, Group and Brenton, James D. and Brinton, Louise A. and Brooks-Wilson, Angela and Brown, Robert and Butzow, Ralf and Campbell, Ian and Carney, Michael E. and Carvalho, Renato S. and Chang-Claude, Jenny and Chen, Ya Anne and Chen, Zhihua and Chow, Wong-Ho and Cicek, Mine S. and Coetzee, Gerhard and Bois, A. du and Cook, Linda S. and Cramer, Daniel W. and Cybulski, Cezary and Dansonka-Mieszkowska, Agnieszka and Doerk, Thilo and Dörk, Thilo and Despierre, Evelyn and Duerst, Matthias and Doherty, Jennifer A. and Dürst, Matthias and Eccles, Diana and Edwards, Robert and Dork, Thilo and Ekici, Arif B. and Fasching, Peter A. and Durst, Matthias and Fenstermacher, David and Flanagan, James and Gao, Yu-Tang and Garcia-Closas, Montserrat and Gentry-Maharaj, Aleksandra and Giles, Graham and Gjyshi, Anxhela and Gore, Martin and Gronwald, Jacek and Høgdall, Estrid and Guo, Qi and Halle, Mari K. and Høgdall, Claus K. and van Altena, Anne M. and Harter, Philipp and van den Berg, David and Hein, Alexander and Heitz, Florian and Hillemanns, Peter and Hoatlin, Maureen and Hosono, Satoyo and Jakubowska, Anna and Du Bois, A. and Jensen, Allan and Kalli, Kimberly R. and Karlan, Beth Y. and Kelemen, Linda E. and Kiemeney, Lambertus A. L. M. and Kjaer, Susanne Krüger and Konecny, Gottfried E. and Krakstad, Camilla and Kupryjanczyk, Jolanta and Matsuo, Keitaro and Lambrechts, Diether and McGuire, Valerie and Lambrechts, Sandrina and McLaughlin, John R. and Le, Nhu D. and Menon, Usha and Lee, Nathan and Modugno, Francesmary and Moysich, Kirsten B. and Lee, Janet van der and Leminen, Arto and Nakanishi, Toru and Narod, Steven A. and Lim, Boon Kiong and Ness, Roberta B. and Lissowska, Jolanta and Nevanlinna, Heli and Lubinski, Jan and Nickels, Stefan and Lundvall, Lene and Noushmehr, Houtan and Hogdall, Estrid and Lurie, Galina and Odunsi, Kunle and Olson, Sara and Massuger, Leon F. A. G. and Hogdall, Claus K. and Orlow, Irene and Paul, James and Pejovic, Tanja and Pelttari, Liisa M. and Permuth-Wey, Jenny and Pike, Malcolm C. and Poole, Elizabeth M. and Qu, Xiaotao and Risch, Harvey A. and Rodriguez-Rodriguez, Lorna and Rossing, Mary Anne and Rudolph, Anja and Runnebaum, Ingo and Rzepecka, Iwona K. and Salvesen, Helga B. and Schwaab, Ira and Severi, Gianluca and Shen, Hui and Shridhar, Vijayalakshmi and Shu, Xiao-Ou and Sieh, Weiva and Southey, Melissa C. and Spellman, Paul and Tajima, Kazuo and Teo, Soo-Hwang and Terry, Kathryn L. and Thompson, Pamela J. and Timorek, Agnieszka and Tworoger, Shelley S. and Van Altena, A. M. and Van Den Berg, D. and Vergote, Ignace and Vierkant, Robert A. and Vitonis, Allison F. and Wang-Gohrke, Shan and Wentzensen, Nicolas and Whittemore, Alice S. and Wik, Elisabeth and Winterhoff, Boris and Woo, Yin Ling and Wu, Anna H. and Yang, Hannah P. and Zheng, Wei and Ziogas, Argyrios and Zulkifli, Famida and Goodman, Marc T. and Hall, Per and Easton, Douglas F. and Pearce, Celeste L. and Berchuck, Andrew and Chenevix-Trench, Georgia and Iversen, Edwin and Monteiro, Alvaro N. A. and Gayther, Simon A. and Schildkraut, Joellen M. and Altena, A. M. van and Sellers, Thomas A.},
  doi = {10.1038/ng.2564},
  journal = {Nature Genetics},
  month = {jan},
  pages = {362-370},
  title = {GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer},
  url = {http://www.nature.com/articles/ng.2564.pdf},
  volume = {45},
  year = {2013}
}

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

Journal article published in 2013 by Paul D. Pdp 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, stralian Cancer Study, Daniel Vincent, Julie M. Cunningham, stralian Ovarian Cancer Study Group, Joe Dennis, Ed Dicks, Katja K. H. Aben, Hoda Anton-Culver, Natalia Antonenkova, Sebastian M. Armasu, Laura Baglietto, Elisa V. Bandera, Andreas du Bois, Study Australian Cancer, Matthias W. Beckmann, Michael J. Birrer, Y. Anne Chen, Greg Bloom, Natalia Bogdanova, Group Australian Ovarian Cancer Study, James D. Brenton, Louise A. Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Butzow, Ian Campbell, Michael E. Carney, Renato S. Carvalho, Jenny Chang-Claude, Ya Anne Chen, Zhihua Chen, Wong-Ho Chow, Mine S. Cicek, Gerhard Coetzee, A. du Bois, Linda S. Cook, Daniel W. Cramer, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Thilo Doerk, Thilo Dörk, Evelyn Despierre, Matthias Duerst, Jennifer A. Doherty, Matthias Dürst, Diana Eccles, Robert Edwards, Thilo Dork, Arif B. Ekici, Peter A. Fasching, Matthias Durst, David Fenstermacher, James Flanagan, Yu-Tang Gao, Montserrat Garcia-Closas, Aleksandra Gentry-Maharaj, Graham Giles, Anxhela Gjyshi, Martin Gore, Jacek Gronwald, Estrid Høgdall, Qi Guo, Mari K. Halle, Claus K. Høgdall, Anne M. van Altena, Philipp Harter, David van den Berg, Alexander Hein, Florian Heitz, Peter Hillemanns, Maureen Hoatlin, Satoyo Hosono, Anna Jakubowska, A. Du Bois, Allan Jensen, Kimberly R. Kalli, Beth Y. Karlan, Linda E. Kelemen, Lambertus A. L. M. Kiemeney, Susanne Krüger Kjaer, Gottfried E. Konecny, Camilla Krakstad, Jolanta Kupryjanczyk, Keitaro Matsuo

, Diether Lambrechts

, Valerie McGuire, Sandrina Lambrechts, John R. McLaughlin, Nhu D. Le, Usha Menon, Nathan Lee, Francesmary Modugno, Kirsten B. Moysich, Janet van der Lee, Arto Leminen, Toru Nakanishi, Steven A. Narod, Boon Kiong Lim, Roberta B. Ness, Jolanta Lissowska, Heli Nevanlinna, Jan Lubinski, Stefan Nickels, Lene Lundvall, Houtan Noushmehr, Estrid Hogdall

, Galina Lurie, Kunle Odunsi, Sara Olson, Leon F. A. G. Massuger, Claus K. Hogdall, 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

, A. M. Van Altena, D. 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, A. M. van Altena, Thomas A. Sellers

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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 x 10(-9)) and 10p12 (rs1243180, P = 1.8 x 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 x 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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GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

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