Genome-wide significant risk associations for mucinous ovarian carcinoma

Linda Kelemen; Kate Lawrenson; Jonathan Tyrer; Qiyuan Li; Janet Lee; Ji-Heui Seo; Catherine M Phelan; Jonathan Beesley; Xiaoqing Chen; Tassja J Spindler; Katja K Aben; Hoda Anton-Culver; Natalia Antonenkova; Helen Baker; Elisa Bandera; Yukie Tarumi Bean; Matthias Beckmann; Maria Bisogna; Line Bjorge; Natalia Bogdanova; Louise Brinton; Angela Brooks-Wilson; Fiona Bruinsma; Ralf Butzow; Ian G Campbell; Karen Carty; Jenny Chang-Claude; Y Anne Chen; Zhihua Chen; Linda Cook; Daniel Cramer; Julie Cunningham; Cezary Cybulski; Agnieszka Dansonka-Mieszkowska; Joe Dennis; Ed Dicks; Jennifer Doherty; Thilo Dork; Andreas Du Bois; Matthias Durst; Diana M Eccles; Douglas F Easton; Robert Edwards; Ursula Eilber; Arif B Ekici; Svend Aage Engelholm; Peter Fasching; Brooke Fridley; Yu-Tang Gao; Aleksandra Gentry-Maharaj; Graham G Giles; Rosalind M Glasspool; Ellen L Goode; Marc T Goodman; Jacek Grownwald; Patricia Harrington; Philipp Harter; Hanis Nazihah Hasmad; Alexander Hein; Florian Heitz; Michelle A T Hildebrandt; Peter Hillemanns; Estrid Hogdall; Claus Hogdall; Satoyo Hosono; Edwin Iversen; Anna Jakubowska; Allan Jensen; Bu-tian Ji; Beth Karlan; Melissa Kellar; Joseph Kelley; Lambertus Kiemeney; Camilla Krakstad; Susanne Kruger Ruger Kjaer; Jolanta Kupryjanczyk; Diether Lambrechts; Sandrina Lambrechts; Nhu Le; Alice W Lee; Shashi Lele; Arto Leminen; Jenny Lester; Douglas Levine; Dong Liang; Jolanta Lissowska; Karen Lu; Jan Lubinski; Lene Lundvall; Leon F A G Massuger; Keitaro Matsuo; Valerie McGuire; John R McLaughlin; Iain A McNeish; Usha N Menon; Francesmary Modugno; Joanna Moes-Sosnowska; Kirsten B Moysich; Steven A Narod; Lotte Nedergaard; Roberta B Ness; Heli Nevanlinna; Noor A M Adenan; Kunle Odunsi; Sara H Olson; Irene Orlow; Sandra Orsulic; Rachel Palmieri Weber; James Paul; Celeste L Pearce; Tanja Pejovic; Liisa M Pelttari; Jenny Permuth-Wey; Malcolm C Pike; Elizabeth M Poole; Susan J Ramus; Harvey A Risch; Barry Rosen; Mary Anne Rossing; Joseph H Rothstein; Anja Rudolph; Ingo B Runnebaum; Iwona K Rzepecka; Helga Birgitte Salvesen; Joellen M Schildkraut; Ira Schwaab; Xiao-Ou Shu; Yurii B Shvetsov; Nadeem Siddiqui; Weiva Sieh; Honglin Song; Melissa Caroline Southey; Lara E Sucheston; Ingvild L Tangen; Soo-Hwang Teo; Kathryn L Terry; Pamela J Thompson; Shelley S Tworoger; Anne M Van Altena; Els Van Nieuwenhuysen; Ignace Vergote; Robert A Vierkant; Shan Wang-Gohrke; Christine S Walsh; Nicolas Wentzensen; Alice S Whittemore; Kristine G Wicklund; Lynne Wilkens; Wlodzimierz Sawicki; Yin Ling Woo; Xifeng Wu; Anna H Wu; Hannah P Yang; Wei Zheng; Argyrios Ziogas; Thomas A Sellers; Matthew L Freedman; Georgia Chenevix-Trench; Paul D P Pharoah; Simon A Gayther; Andrew Berchuck

doi:10.1038/ng.3336

Genome-wide significant risk associations for mucinous ovarian carcinoma

Linda Kelemen, Kate Lawrenson, Jonathan Tyrer, Qiyuan Li, Janet Lee, Ji-Heui Seo, Catherine M Phelan, Jonathan Beesley, Xiaoqing Chen, Tassja J Spindler, Katja K Aben, Hoda Anton-Culver, Natalia Antonenkova, Helen Baker, Elisa Bandera, Yukie Tarumi Bean, Matthias Beckmann, Maria Bisogna, Line Bjorge, Natalia BogdanovaLouise Brinton, Angela Brooks-Wilson, Fiona Bruinsma, Ralf Butzow, Ian G Campbell, Karen Carty, Jenny Chang-Claude, Y Anne Chen, Zhihua Chen, Linda Cook, Daniel Cramer, Julie Cunningham, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Joe Dennis, Ed Dicks, Jennifer Doherty, Thilo Dork, Andreas Du Bois, Matthias Durst, Diana M Eccles, Douglas F Easton, Robert Edwards, Ursula Eilber, Arif B Ekici, Svend Aage Engelholm, Peter Fasching, Brooke Fridley, Yu-Tang Gao, Aleksandra Gentry-Maharaj, Graham G Giles, Rosalind M Glasspool, Ellen L Goode, Marc T Goodman, Jacek Grownwald, Patricia Harrington, Philipp Harter, Hanis Nazihah Hasmad, Alexander Hein, Florian Heitz, Michelle A T Hildebrandt, Peter Hillemanns, Estrid Hogdall, Claus Hogdall, Satoyo Hosono, Edwin Iversen, Anna Jakubowska, Allan Jensen, Bu-tian Ji, Beth Karlan, Melissa Kellar, Joseph Kelley, Lambertus Kiemeney, Camilla Krakstad, Susanne Kruger Ruger Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu Le, Alice W Lee, Shashi Lele, Arto Leminen, Jenny Lester, Douglas Levine, Dong Liang, Jolanta Lissowska, Karen Lu, Jan Lubinski, Lene Lundvall, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R McLaughlin, Iain A McNeish, Usha N Menon, Francesmary Modugno, Joanna Moes-Sosnowska, Kirsten B Moysich, Steven A Narod, Lotte Nedergaard, Roberta B Ness, Heli Nevanlinna, Noor A M Adenan, Kunle Odunsi, Sara H Olson, Irene Orlow, Sandra Orsulic, Rachel Palmieri Weber, James Paul, Celeste L Pearce, Tanja Pejovic, Liisa M Pelttari, Jenny Permuth-Wey, Malcolm C Pike, Elizabeth M Poole, Susan J Ramus, Harvey A Risch, Barry Rosen, Mary Anne Rossing, Joseph H Rothstein, Anja Rudolph, Ingo B Runnebaum, Iwona K Rzepecka, Helga Birgitte Salvesen, Joellen M Schildkraut, Ira Schwaab, Xiao-Ou Shu, Yurii B Shvetsov, Nadeem Siddiqui, Weiva Sieh, Honglin Song, Melissa Caroline Southey, Lara E Sucheston, Ingvild L Tangen, Soo-Hwang Teo, Kathryn L Terry, Pamela J Thompson, Shelley S Tworoger, Anne M Van Altena, Els Van Nieuwenhuysen, Ignace Vergote, Robert A Vierkant, Shan Wang-Gohrke, Christine S Walsh, Nicolas Wentzensen, Alice S Whittemore, Kristine G Wicklund, Lynne Wilkens, Wlodzimierz Sawicki, Yin Ling Woo, Xifeng Wu, Anna H Wu, Hannah P Yang, Wei Zheng, Argyrios Ziogas, Thomas A Sellers, Matthew L Freedman, Georgia Chenevix-Trench, Paul D P Pharoah, Simon A Gayther, Andrew Berchuck

Epidemiology and Preventive Medicine Alfred Hospital

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

65 Citations (Scopus)

Abstract

Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 ? 10-8), rs711830 at 2q31.1 (P = 7.5 ? 10-12) and rs688187 at 19q13.2 (P = 6.8 ? 10-13). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 ? 10-4, false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.

Original language	English
Pages (from-to)	888 - 897
Number of pages	10
Journal	Nature Genetics
Volume	47
Issue number	8
DOIs	https://doi.org/10.1038/ng.3336
Publication status	Published - 2015

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10.1038/ng.3336

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Kelemen, L., Lawrenson, K., Tyrer, J., Li, Q., Lee, J., Seo, J-H., Phelan, C. M., Beesley, J., Chen, X., Spindler, T. J., Aben, K. K., Anton-Culver, H., Antonenkova, N., Baker, H., Bandera, E., Bean, Y. T., Beckmann, M., Bisogna, M., Bjorge, L., ... Berchuck, A. (2015). Genome-wide significant risk associations for mucinous ovarian carcinoma. Nature Genetics, 47(8), 888 - 897. https://doi.org/10.1038/ng.3336

@article{120bc67e73ec4364ad4d10ec0c606d48,

title = "Genome-wide significant risk associations for mucinous ovarian carcinoma",

abstract = "Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 ? 10-8), rs711830 at 2q31.1 (P = 7.5 ? 10-12) and rs688187 at 19q13.2 (P = 6.8 ? 10-13). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 ? 10-4, false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.",

author = "Linda Kelemen and Kate Lawrenson and Jonathan Tyrer and Qiyuan Li and Janet Lee and Ji-Heui Seo and Phelan, {Catherine M} and Jonathan Beesley and Xiaoqing Chen and Spindler, {Tassja J} and Aben, {Katja K} and Hoda Anton-Culver and Natalia Antonenkova and Helen Baker and Elisa Bandera and Bean, {Yukie Tarumi} and Matthias Beckmann and Maria Bisogna and Line Bjorge and Natalia Bogdanova and Louise Brinton and Angela Brooks-Wilson and Fiona Bruinsma and Ralf Butzow and Campbell, {Ian G} and Karen Carty and Jenny Chang-Claude and Chen, {Y Anne} and Zhihua Chen and Linda Cook and Daniel Cramer and Julie Cunningham and Cezary Cybulski and Agnieszka Dansonka-Mieszkowska and Joe Dennis and Ed Dicks and Jennifer Doherty and Thilo Dork and {Du Bois}, Andreas and Matthias Durst and Eccles, {Diana M} and Easton, {Douglas F} and Robert Edwards and Ursula Eilber and Ekici, {Arif B} and Engelholm, {Svend Aage} and Peter Fasching and Brooke Fridley and Yu-Tang Gao and Aleksandra Gentry-Maharaj and Giles, {Graham G} and Glasspool, {Rosalind M} and Goode, {Ellen L} and Goodman, {Marc T} and Jacek Grownwald and Patricia Harrington and Philipp Harter and Hasmad, {Hanis Nazihah} and Alexander Hein and Florian Heitz and Hildebrandt, {Michelle A T} and Peter Hillemanns and Estrid Hogdall and Claus Hogdall and Satoyo Hosono and Edwin Iversen and Anna Jakubowska and Allan Jensen and Bu-tian Ji and Beth Karlan and Melissa Kellar and Joseph Kelley and Lambertus Kiemeney and Camilla Krakstad and Kjaer, {Susanne Kruger Ruger} and Jolanta Kupryjanczyk and Diether Lambrechts and Sandrina Lambrechts and Nhu Le and Lee, {Alice W} and Shashi Lele and Arto Leminen and Jenny Lester and Douglas Levine and Dong Liang and Jolanta Lissowska and Karen Lu and Jan Lubinski and Lene Lundvall and Massuger, {Leon F A G} and Keitaro Matsuo and Valerie McGuire and McLaughlin, {John R} and McNeish, {Iain A} and Menon, {Usha N} and Francesmary Modugno and Joanna Moes-Sosnowska and Moysich, {Kirsten B} and Narod, {Steven A} and Lotte Nedergaard and Ness, {Roberta B} and Heli Nevanlinna and Adenan, {Noor A M} and Kunle Odunsi and Olson, {Sara H} and Irene Orlow and Sandra Orsulic and Weber, {Rachel Palmieri} and James Paul and Pearce, {Celeste L} and Tanja Pejovic and Pelttari, {Liisa M} and Jenny Permuth-Wey and Pike, {Malcolm C} and Poole, {Elizabeth M} and Ramus, {Susan J} and Risch, {Harvey A} and Barry Rosen and Rossing, {Mary Anne} and Rothstein, {Joseph H} and Anja Rudolph and Runnebaum, {Ingo B} and Rzepecka, {Iwona K} and Salvesen, {Helga Birgitte} and Schildkraut, {Joellen M} and Ira Schwaab and Xiao-Ou Shu and Shvetsov, {Yurii B} and Nadeem Siddiqui and Weiva Sieh and Honglin Song and Southey, {Melissa Caroline} and Sucheston, {Lara E} and Tangen, {Ingvild L} and Soo-Hwang Teo and Terry, {Kathryn L} and Thompson, {Pamela J} and Tworoger, {Shelley S} and {Van Altena}, {Anne M} and {Van Nieuwenhuysen}, Els and Ignace Vergote and Vierkant, {Robert A} and Shan Wang-Gohrke and Walsh, {Christine S} and Nicolas Wentzensen and Whittemore, {Alice S} and Wicklund, {Kristine G} and Lynne Wilkens and Wlodzimierz Sawicki and Woo, {Yin Ling} and Xifeng Wu and Wu, {Anna H} and Yang, {Hannah P} and Wei Zheng and Argyrios Ziogas and Sellers, {Thomas A} and Freedman, {Matthew L} and Georgia Chenevix-Trench and Pharoah, {Paul D P} and Gayther, {Simon A} and Andrew Berchuck",

year = "2015",

doi = "10.1038/ng.3336",

language = "English",

volume = "47",

pages = "888 -- 897",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "8",

}

Kelemen, L, Lawrenson, K, Tyrer, J, Li, Q, Lee, J, Seo, J-H, Phelan, CM, Beesley, J, Chen, X, Spindler, TJ, Aben, KK, Anton-Culver, H, Antonenkova, N, Baker, H, Bandera, E, Bean, YT, Beckmann, M, Bisogna, M, Bjorge, L, Bogdanova, N, Brinton, L, Brooks-Wilson, A, Bruinsma, F, Butzow, R, Campbell, IG, Carty, K, Chang-Claude, J, Chen, YA, Chen, Z, Cook, L, Cramer, D, Cunningham, J, Cybulski, C, Dansonka-Mieszkowska, A, Dennis, J, Dicks, E, Doherty, J, Dork, T, Du Bois, A, Durst, M, Eccles, DM, Easton, DF, Edwards, R, Eilber, U, Ekici, AB, Engelholm, SA, Fasching, P, Fridley, B, Gao, Y-T, Gentry-Maharaj, A, Giles, GG, Glasspool, RM, Goode, EL, Goodman, MT, Grownwald, J, Harrington, P, Harter, P, Hasmad, HN, Hein, A, Heitz, F, Hildebrandt, MAT, Hillemanns, P, Hogdall, E, Hogdall, C, Hosono, S, Iversen, E, Jakubowska, A, Jensen, A, Ji, B, Karlan, B, Kellar, M, Kelley, J, Kiemeney, L, Krakstad, C, Kjaer, SKR, Kupryjanczyk, J, Lambrechts, D, Lambrechts, S, Le, N, Lee, AW, Lele, S, Leminen, A, Lester, J, Levine, D, Liang, D, Lissowska, J, Lu, K, Lubinski, J, Lundvall, L, Massuger, LFAG, Matsuo, K, McGuire, V, McLaughlin, JR, McNeish, IA, Menon, UN, Modugno, F, Moes-Sosnowska, J, Moysich, KB, Narod, SA, Nedergaard, L, Ness, RB, Nevanlinna, H, Adenan, NAM, Odunsi, K, Olson, SH, Orlow, I, Orsulic, S, Weber, RP, Paul, J, Pearce, CL, Pejovic, T, Pelttari, LM, Permuth-Wey, J, Pike, MC, Poole, EM, Ramus, SJ, Risch, HA, Rosen, B, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, IB, Rzepecka, IK, Salvesen, HB, Schildkraut, JM, Schwaab, I, Shu, X-O, Shvetsov, YB, Siddiqui, N, Sieh, W, Song, H, Southey, MC, Sucheston, LE, Tangen, IL, Teo, S-H, Terry, KL, Thompson, PJ, Tworoger, SS, Van Altena, AM, Van Nieuwenhuysen, E, Vergote, I, Vierkant, RA, Wang-Gohrke, S, Walsh, CS, Wentzensen, N, Whittemore, AS, Wicklund, KG, Wilkens, L, Sawicki, W, Woo, YL, Wu, X, Wu, AH, Yang, HP, Zheng, W, Ziogas, A, Sellers, TA, Freedman, ML, Chenevix-Trench, G, Pharoah, PDP, Gayther, SA & Berchuck, A 2015, 'Genome-wide significant risk associations for mucinous ovarian carcinoma', Nature Genetics, vol. 47, no. 8, pp. 888 - 897. https://doi.org/10.1038/ng.3336

TY - JOUR

T1 - Genome-wide significant risk associations for mucinous ovarian carcinoma

AU - Kelemen, Linda

AU - Lawrenson, Kate

AU - Tyrer, Jonathan

AU - Li, Qiyuan

AU - Lee, Janet

AU - Seo, Ji-Heui

AU - Phelan, Catherine M

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - Spindler, Tassja J

AU - Aben, Katja K

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia

AU - Baker, Helen

AU - Bandera, Elisa

AU - Bean, Yukie Tarumi

AU - Beckmann, Matthias

AU - Bisogna, Maria

AU - Bjorge, Line

AU - Bogdanova, Natalia

AU - Brinton, Louise

AU - Brooks-Wilson, Angela

AU - Bruinsma, Fiona

AU - Butzow, Ralf

AU - Campbell, Ian G

AU - Carty, Karen

AU - Chang-Claude, Jenny

AU - Chen, Y Anne

AU - Chen, Zhihua

AU - Cook, Linda

AU - Cramer, Daniel

AU - Cunningham, Julie

AU - Cybulski, Cezary

AU - Dansonka-Mieszkowska, Agnieszka

AU - Dennis, Joe

AU - Dicks, Ed

AU - Doherty, Jennifer

AU - Dork, Thilo

AU - Du Bois, Andreas

AU - Durst, Matthias

AU - Eccles, Diana M

AU - Easton, Douglas F

AU - Edwards, Robert

AU - Eilber, Ursula

AU - Ekici, Arif B

AU - Engelholm, Svend Aage

AU - Fasching, Peter

AU - Fridley, Brooke

AU - Gao, Yu-Tang

AU - Gentry-Maharaj, Aleksandra

AU - Giles, Graham G

AU - Glasspool, Rosalind M

AU - Goode, Ellen L

AU - Goodman, Marc T

AU - Grownwald, Jacek

AU - Harrington, Patricia

AU - Harter, Philipp

AU - Hasmad, Hanis Nazihah

AU - Hein, Alexander

AU - Heitz, Florian

AU - Hildebrandt, Michelle A T

AU - Hillemanns, Peter

AU - Hogdall, Estrid

AU - Hogdall, Claus

AU - Hosono, Satoyo

AU - Iversen, Edwin

AU - Jakubowska, Anna

AU - Jensen, Allan

AU - Ji, Bu-tian

AU - Karlan, Beth

AU - Kellar, Melissa

AU - Kelley, Joseph

AU - Kiemeney, Lambertus

AU - Krakstad, Camilla

AU - Kjaer, Susanne Kruger Ruger

AU - Kupryjanczyk, Jolanta

AU - Lambrechts, Diether

AU - Lambrechts, Sandrina

AU - Le, Nhu

AU - Lee, Alice W

AU - Lele, Shashi

AU - Leminen, Arto

AU - Lester, Jenny

AU - Levine, Douglas

AU - Liang, Dong

AU - Lissowska, Jolanta

AU - Lu, Karen

AU - Lubinski, Jan

AU - Lundvall, Lene

AU - Massuger, Leon F A G

AU - Matsuo, Keitaro

AU - McGuire, Valerie

AU - McLaughlin, John R

AU - McNeish, Iain A

AU - Menon, Usha N

AU - Modugno, Francesmary

AU - Moes-Sosnowska, Joanna

AU - Moysich, Kirsten B

AU - Narod, Steven A

AU - Nedergaard, Lotte

AU - Ness, Roberta B

AU - Nevanlinna, Heli

AU - Adenan, Noor A M

AU - Odunsi, Kunle

AU - Olson, Sara H

AU - Orlow, Irene

AU - Orsulic, Sandra

AU - Weber, Rachel Palmieri

AU - Paul, James

AU - Pearce, Celeste L

AU - Pejovic, Tanja

AU - Pelttari, Liisa M

AU - Permuth-Wey, Jenny

AU - Pike, Malcolm C

AU - Poole, Elizabeth M

AU - Ramus, Susan J

AU - Risch, Harvey A

AU - Rosen, Barry

AU - Rossing, Mary Anne

AU - Rothstein, Joseph H

AU - Rudolph, Anja

AU - Runnebaum, Ingo B

AU - Rzepecka, Iwona K

AU - Salvesen, Helga Birgitte

AU - Schildkraut, Joellen M

AU - Schwaab, Ira

AU - Shu, Xiao-Ou

AU - Shvetsov, Yurii B

AU - Siddiqui, Nadeem

AU - Sieh, Weiva

AU - Song, Honglin

AU - Southey, Melissa Caroline

AU - Sucheston, Lara E

AU - Tangen, Ingvild L

AU - Teo, Soo-Hwang

AU - Terry, Kathryn L

AU - Thompson, Pamela J

AU - Tworoger, Shelley S

AU - Van Altena, Anne M

AU - Van Nieuwenhuysen, Els

AU - Vergote, Ignace

AU - Vierkant, Robert A

AU - Wang-Gohrke, Shan

AU - Walsh, Christine S

AU - Wentzensen, Nicolas

AU - Whittemore, Alice S

AU - Wicklund, Kristine G

AU - Wilkens, Lynne

AU - Sawicki, Wlodzimierz

AU - Woo, Yin Ling

AU - Wu, Xifeng

AU - Wu, Anna H

AU - Yang, Hannah P

AU - Zheng, Wei

AU - Ziogas, Argyrios

AU - Sellers, Thomas A

AU - Freedman, Matthew L

AU - Chenevix-Trench, Georgia

AU - Pharoah, Paul D P

AU - Gayther, Simon A

AU - Berchuck, Andrew

PY - 2015

Y1 - 2015

N2 - Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 ? 10-8), rs711830 at 2q31.1 (P = 7.5 ? 10-12) and rs688187 at 19q13.2 (P = 6.8 ? 10-13). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 ? 10-4, false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.

AB - Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 ? 10-8), rs711830 at 2q31.1 (P = 7.5 ? 10-12) and rs688187 at 19q13.2 (P = 6.8 ? 10-13). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 ? 10-4, false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk-associated SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.

UR - http://www.nature.com.ezproxy.lib.monash.edu.au/ng/journal/v47/n8/extref/ng.3336-S1.pdf

U2 - 10.1038/ng.3336

DO - 10.1038/ng.3336

M3 - Article

VL - 47

SP - 888

EP - 897

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 8

ER -

Genome-wide significant risk associations for mucinous ovarian carcinoma

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