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

Paul D Pharoah; Ya-Yu Tsai; Susan J Ramus; Catherine M Phelan; Ellen L Goode; Kate Lawrenson; Melissa Buckley; Brooke Fridley; Jonathan Tyrer; Howard Shen; Rachel Weber; Rod Karevan; Melissa Larson; Honglin Song; Daniel Tessier; Francois Bacot; Daniel Vincent; Julie Cunningham; Joe Dennis; Ed Dicks; Katja K Aben; Hoda Anton-Culver; Natalia Antonenkova; Sebastian Armasu; Laura Baglietto; Elisa Bandera; Matthias Beckmann; Michael Birrer; Greg Bloom; Natalia Bogdanova; James D Brenton; Louise Brinton; Angela Brooks-Wilson; Robert Brown; Ralf Butzow; Ian G Campbell; Michael Carney; Renato Carvalho; Jenny Chang-Claude; Y Anne Chen; Zhihua Chen; Wong-Ho Chow; Mine S Cicek; Gerhard Coetzee; Linda Cook; Daniel Cramer; Cezary Cybulski; Agnieszka Dansonka-Mieszkowska; Evelyn Despierre; Jennifer Doherty; Thilo Dork; Andreas Du Bois; Matthias Duerst; Diana M Eccles; Robert Edwards; Arif B Ekici; Peter 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 Halle; Philipp Harter; Alexander Hein; Florian Heitz; Peter Hillemanns; Maureen Hoatlin; Estrid Hogdall; Claus Hogdall; Satoyo Hosono; Anna Jakubowska; Allan Jensen; Kimberly Kalli; Beth Karlan; Linda Kelemen; Lambertus Kiemeney; Susanne Kruger Kjaer; Gottfried E Konecny; Camilla Krakstad; Jolanta Kupryjanczyk; Diether Lambrechts; Sandrina Lambrechts; Nhu Le; Nathan Lee; Janet Lee; Arto Leminen; Boon Kiong Lim; Jolanta Lissowska; Jan Lubinski; Lene Lundvall; Galina Lurie; Leon F A G Massuger; Keitaro Matsuo; Valerie McGuire; John R McLaughlin; Usha N Menon; Francesmary Modugno; Kirsten B Moysich; Toru Nakanishi; Steven A Narod; Roberta B Ness; Heli Nevanlinna; Stefan Nickels; Houtan Noushmehr; Kunle Odunsi; Sara H 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 B 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 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 Pharoah, Ya-Yu Tsai, Susan J Ramus, Catherine M Phelan, Ellen L Goode, Kate Lawrenson, Melissa Buckley, Brooke Fridley, Jonathan Tyrer, Howard Shen, Rachel Weber, Rod Karevan, Melissa Larson, Honglin Song, Daniel Tessier, Francois Bacot, Daniel Vincent, Julie Cunningham, Joe Dennis, Ed DicksKatja K Aben, Hoda Anton-Culver, Natalia Antonenkova, Sebastian Armasu, Laura Baglietto, Elisa Bandera, Matthias Beckmann, Michael Birrer, Greg Bloom, Natalia Bogdanova, James D Brenton, Louise Brinton, Angela Brooks-Wilson, Robert Brown, Ralf Butzow, Ian G Campbell, Michael Carney, Renato Carvalho, Jenny Chang-Claude, Y Anne Chen, Zhihua Chen, Wong-Ho Chow, Mine S Cicek, Gerhard Coetzee, Linda Cook, Daniel Cramer, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Evelyn Despierre, Jennifer Doherty, Thilo Dork, Andreas Du Bois, Matthias Duerst, Diana M Eccles, Robert Edwards, Arif B Ekici, Peter 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 Halle, Philipp Harter, Alexander Hein, Florian Heitz, Peter Hillemanns, Maureen Hoatlin, Estrid Hogdall, Claus Hogdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Kimberly Kalli, Beth Karlan, Linda Kelemen, Lambertus Kiemeney, Susanne Kruger Kjaer, Gottfried E Konecny, Camilla Krakstad, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu Le, Nathan Lee, Janet Lee, Arto Leminen, Boon Kiong Lim, Jolanta Lissowska, Jan Lubinski, Lene Lundvall, Galina Lurie, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R McLaughlin, Usha N Menon, Francesmary Modugno, Kirsten B Moysich, Toru Nakanishi, Steven A Narod, Roberta B Ness, Heli Nevanlinna, Stefan Nickels, Houtan Noushmehr, Kunle Odunsi, Sara H 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 B 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 Monteiro, Simon A Gayther, Joellen M Schildkraut, Thomas A Sellers

Epidemiology and Preventive Medicine Alfred Hospital

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

302 Citations (Scopus)

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
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
Publication status	Published - 2013

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10.1038/ng.2564

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Pharoah, P. D., Tsai, Y.-Y., Ramus, S. J., Phelan, C. M., Goode, E. L., Lawrenson, K., Buckley, M., Fridley, B., Tyrer, J., Shen, H., Weber, R., Karevan, R., Larson, M., Song, H., Tessier, D., Bacot, F., Vincent, D., Cunningham, J., 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

@article{363824ca18df42f8b0b86b96da202ea7,

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} and Ya-Yu Tsai and Ramus, {Susan J} and Phelan, {Catherine M} and Goode, {Ellen L} and Kate Lawrenson and Melissa Buckley and Brooke Fridley and Jonathan Tyrer and Howard Shen and Rachel Weber and Rod Karevan and Melissa Larson and Honglin Song and Daniel Tessier and Francois Bacot and Daniel Vincent and Julie Cunningham and Joe Dennis and Ed Dicks and Aben, {Katja K} and Hoda Anton-Culver and Natalia Antonenkova and Sebastian Armasu and Laura Baglietto and Elisa Bandera and Matthias Beckmann and Michael Birrer and Greg Bloom and Natalia Bogdanova and Brenton, {James D} and Louise Brinton and Angela Brooks-Wilson and Robert Brown and Ralf Butzow and Campbell, {Ian G} and Michael Carney and Renato Carvalho and Jenny Chang-Claude and Chen, {Y Anne} and Zhihua Chen and Wong-Ho Chow and Cicek, {Mine S} and Gerhard Coetzee and Linda Cook and Daniel Cramer and Cezary Cybulski and Agnieszka Dansonka-Mieszkowska and Evelyn Despierre and Jennifer Doherty and Thilo Dork and {Du Bois}, Andreas and Matthias Duerst and Eccles, {Diana M} and Robert Edwards and Ekici, {Arif B} and Peter Fasching and David Fenstermacher and James Flanagan and Yu-Tang Gao and Montserrat Garcia-Closas and Aleksandra Gentry-Maharaj and Graham Giles and Anxhela Gjyshi and Martin Gore and Jacek Gronwald and Qi Guo and Mari Halle and Philipp Harter and Alexander Hein and Florian Heitz and Peter Hillemanns and Maureen Hoatlin and Estrid Hogdall and Claus Hogdall and Satoyo Hosono and Anna Jakubowska and Allan Jensen and Kimberly Kalli and Beth Karlan and Linda Kelemen and Lambertus Kiemeney and Kjaer, {Susanne Kruger} and Konecny, {Gottfried E} and Camilla Krakstad and Jolanta Kupryjanczyk and Diether Lambrechts and Sandrina Lambrechts and Nhu Le and Nathan Lee and Janet Lee and Arto Leminen and Lim, {Boon Kiong} and Jolanta Lissowska and Jan Lubinski and Lene Lundvall and Galina Lurie and Massuger, {Leon F A G} and Keitaro Matsuo and Valerie McGuire and McLaughlin, {John R} and Menon, {Usha N} 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 Olson, {Sara H} 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 Runnebaum, {Ingo B} and Rzepecka, {Iwona K} and Salvesen, {Helga B} and Ira Schwaab and Gianluca Severi and Hui Shen and Vijayalakshmi Shridhar and Xiao-Ou Shu and Weiva Sieh and Southey, {Melissa C} and Paul Spellman and Kazuo Tajima and Soo-Hwang Teo 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 Alvaro Monteiro and Gayther, {Simon A} and Schildkraut, {Joellen M} and Sellers, {Thomas A}",

year = "2013",

doi = "10.1038/ng.2564",

language = "English",

volume = "45",

pages = "362 -- 370",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "4",

}

Pharoah, PD, Tsai, Y-Y, Ramus, SJ, Phelan, CM, Goode, EL, Lawrenson, K, Buckley, M, Fridley, B, Tyrer, J, Shen, H, Weber, R, Karevan, R, Larson, M, Song, H, Tessier, D, Bacot, F, Vincent, D, Cunningham, J, Dennis, J, Dicks, E, Aben, KK, Anton-Culver, H, Antonenkova, N, Armasu, S, Baglietto, L, Bandera, E, Beckmann, M, Birrer, M, Bloom, G, Bogdanova, N, Brenton, JD, Brinton, L, Brooks-Wilson, A, Brown, R, Butzow, R, Campbell, IG, Carney, M, Carvalho, R, Chang-Claude, J, Chen, YA, Chen, Z, Chow, W-H, Cicek, MS, Coetzee, G, Cook, L, Cramer, D, Cybulski, C, Dansonka-Mieszkowska, A, Despierre, E, Doherty, J, Dork, T, Du Bois, A, Duerst, M, Eccles, DM, Edwards, R, Ekici, AB, Fasching, P, Fenstermacher, D, Flanagan, J, Gao, Y-T, Garcia-Closas, M, Gentry-Maharaj, A, Giles, G, Gjyshi, A, Gore, M, Gronwald, J, Guo, Q, Halle, M, Harter, P, Hein, A, Heitz, F, Hillemanns, P, Hoatlin, M, Hogdall, E, Hogdall, C, Hosono, S, Jakubowska, A, Jensen, A, Kalli, K, Karlan, B, Kelemen, L, Kiemeney, L, Kjaer, SK, Konecny, GE, Krakstad, C, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, N, Lee, N, Lee, J, Leminen, A, Lim, BK, Lissowska, J, Lubinski, J, Lundvall, L, Lurie, G, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, Menon, UN, Modugno, F, Moysich, KB, Nakanishi, T, Narod, SA, Ness, RB, Nevanlinna, H, Nickels, S, Noushmehr, H, Odunsi, K, Olson, SH, 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, IB, Rzepecka, IK, Salvesen, HB, Schwaab, I, Severi, G, Shen, H, Shridhar, V, Shu, X-O, Sieh, W, Southey, MC, Spellman, P, Tajima, K, Teo, S-H, 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, A, 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

TY - JOUR

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

AU - Pharoah, Paul D

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

AU - Tyrer, Jonathan

AU - Shen, Howard

AU - Weber, Rachel

AU - Karevan, Rod

AU - Larson, Melissa

AU - Song, Honglin

AU - Tessier, Daniel

AU - Bacot, Francois

AU - Vincent, Daniel

AU - Cunningham, Julie

AU - Dennis, Joe

AU - Dicks, Ed

AU - Aben, Katja K

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia

AU - Armasu, Sebastian

AU - Baglietto, Laura

AU - Bandera, Elisa

AU - Beckmann, Matthias

AU - Birrer, Michael

AU - Bloom, Greg

AU - Bogdanova, Natalia

AU - Brenton, James D

AU - Brinton, Louise

AU - Brooks-Wilson, Angela

AU - Brown, Robert

AU - Butzow, Ralf

AU - Campbell, Ian G

AU - Carney, Michael

AU - Carvalho, Renato

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

AU - Cramer, Daniel

AU - Cybulski, Cezary

AU - Dansonka-Mieszkowska, Agnieszka

AU - Despierre, Evelyn

AU - Doherty, Jennifer

AU - Dork, Thilo

AU - Du Bois, Andreas

AU - Duerst, Matthias

AU - Eccles, Diana M

AU - Edwards, Robert

AU - Ekici, Arif B

AU - Fasching, Peter

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

AU - Harter, Philipp

AU - Hein, Alexander

AU - Heitz, Florian

AU - Hillemanns, Peter

AU - Hoatlin, Maureen

AU - Hogdall, Estrid

AU - Hogdall, Claus

AU - Hosono, Satoyo

AU - Jakubowska, Anna

AU - Jensen, Allan

AU - Kalli, Kimberly

AU - Karlan, Beth

AU - Kelemen, Linda

AU - Kiemeney, Lambertus

AU - Kjaer, Susanne Kruger

AU - Konecny, Gottfried E

AU - Krakstad, Camilla

AU - Kupryjanczyk, Jolanta

AU - Lambrechts, Diether

AU - Lambrechts, Sandrina

AU - Le, Nhu

AU - Lee, Nathan

AU - Lee, Janet

AU - Leminen, Arto

AU - Lim, Boon Kiong

AU - Lissowska, Jolanta

AU - Lubinski, 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 N

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 H

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 B

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

AU - Gayther, Simon A

AU - Schildkraut, Joellen M

AU - Sellers, Thomas A

PY - 2013

Y1 - 2013

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.

UR - http://www.nature.com/ng/journal/v45/n4/pdf/ng.2564.pdf

U2 - 10.1038/ng.2564

DO - 10.1038/ng.2564

M3 - Article

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

Abstract

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