Identification of nine new susceptibility loci for endometrial cancer

Tracy A. O’Mara; Dylan M. Glubb; Frederic Amant; Daniela Annibali; Katie Ashton; John Attia; Paul L. Auer; Matthias W. Beckmann; Amanda Black; Manjeet K. Bolla; Hiltrud Brauch; Hermann Brenner; Louise Brinton; Daniel D. Buchanan; Barbara Burwinkel; Jenny Chang-Claude; Stephen J. Chanock; Chu Chen; Maxine M. Chen; Timothy H.T. Cheng; Christine L. Clarke; Mark Clendenning; Linda S. Cook; Fergus J. Couch; Angela Cox; Marta Crous-Bous; Kamila Czene; Felix Day; Joe Dennis; Jeroen Depreeuw; Jennifer Anne Doherty; Thilo Dörk; Sean C. Dowdy; Matthias Dürst; Arif B. Ekici; Peter A. Fasching; Brooke L. Fridley; Christine M. Friedenreich; Lin Fritschi; Jenny Fung; Montserrat García-Closas; Mia M. Gaudet; Graham G. Giles; Ellen L. Goode; Maggie Gorman; Christopher A. Haiman; Per Hall; Susan E. Hankison; Catherine S. Healey; Alexander Hein; Peter Hillemanns; Shirley Hodgson; Erling A. Hoivik; Elizabeth G. Holliday; John L. Hopper; David J. Hunter; Angela Jones; Camilla Krakstad; Vessela N. Kristensen; Diether Lambrechts; Loic Le Marchand; Xiaolin Liang; Annika Lindblom; Jolanta Lissowska; Jirong Long; Lingeng Lu; Anthony M. Magliocco; Lynn Martin; Mark McEvoy; Alfons Meindl; Kyriaki Michailidou; Roger L. Milne; Miriam Mints; Grant W. Montgomery; Rami Nassir; Håkan Olsson; Irene Orlow; Geoffrey Otton; Claire Palles; John R.B. Perry; Julian Peto; Loreall Pooler; Jennifer Prescott; Tony Proietto; Timothy R. Rebbeck; Harvey A. Risch; Peter A.W. Rogers; Matthias Rübner; Ingo Runnebaum; Carlotta Sacerdote; Gloria E. Sarto; Fredrick Schumacher; Rodney J. Scott; V. Wendy Setiawan; Mitul Shah; Xin Sheng; Xiao Ou Shu; Melissa C. Southey; Anthony J. Swerdlow; Emma Tham; Jone Trovik; Constance Turman; Jonathan P. Tyrer; Celine Vachon; David VanDen Berg; Adriaan Vanderstichele; Zhaoming Wang; Penelope M. Webb; Nicolas Wentzensen; Henrica M.J. Werner; Stacey J. Winham; Alicja Wolk; Lucy Xia; Yong Bing Xiang; Hannah P. Yang; Herbert Yu; Wei Zheng; Paul D.P. Pharoah; Alison M. Dunning; Peter Kraft; Immaculata De Vivo; Ian Tomlinson; Douglas F. Easton; Amanda B. Spurdle; Deborah J. Thompson

doi:10.1038/s41467-018-05427-7

Identification of nine new susceptibility loci for endometrial cancer

Tracy A. O’Mara, Dylan M. Glubb, Frederic Amant, Daniela Annibali, Katie Ashton, John Attia, Paul L. Auer, Matthias W. Beckmann, Amanda Black, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, Louise Brinton, Daniel D. Buchanan, Barbara Burwinkel, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, Maxine M. Chen, Timothy H.T. ChengChristine L. Clarke, Mark Clendenning, Linda S. Cook, Fergus J. Couch, Angela Cox, Marta Crous-Bous, Kamila Czene, Felix Day, Joe Dennis, Jeroen Depreeuw, Jennifer Anne Doherty, Thilo Dörk, Sean C. Dowdy, Matthias Dürst, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Christine M. Friedenreich, Lin Fritschi, Jenny Fung, Montserrat García-Closas, Mia M. Gaudet, Graham G. Giles, Ellen L. Goode, Maggie Gorman, Christopher A. Haiman, Per Hall, Susan E. Hankison, Catherine S. Healey, Alexander Hein, Peter Hillemanns, Shirley Hodgson, Erling A. Hoivik, Elizabeth G. Holliday, John L. Hopper, David J. Hunter, Angela Jones, Camilla Krakstad, Vessela N. Kristensen, Diether Lambrechts, Loic Le Marchand, Xiaolin Liang, Annika Lindblom, Jolanta Lissowska, Jirong Long, Lingeng Lu, Anthony M. Magliocco, Lynn Martin, Mark McEvoy, Alfons Meindl, Kyriaki Michailidou, Roger L. Milne, Miriam Mints, Grant W. Montgomery, Rami Nassir, Håkan Olsson, Irene Orlow, Geoffrey Otton, Claire Palles, John R.B. Perry, Julian Peto, Loreall Pooler, Jennifer Prescott, Tony Proietto, Timothy R. Rebbeck, Harvey A. Risch, Peter A.W. Rogers, Matthias Rübner, Ingo Runnebaum, Carlotta Sacerdote, Gloria E. Sarto, Fredrick Schumacher, Rodney J. Scott, V. Wendy Setiawan, Mitul Shah, Xin Sheng, Xiao Ou Shu, Melissa C. Southey, Anthony J. Swerdlow, Emma Tham, Jone Trovik, Constance Turman, Jonathan P. Tyrer, Celine Vachon, David VanDen Berg, Adriaan Vanderstichele, Zhaoming Wang, Penelope M. Webb, Nicolas Wentzensen, Henrica M.J. Werner, Stacey J. Winham, Alicja Wolk, Lucy Xia, Yong Bing Xiang, Hannah P. Yang, Herbert Yu, Wei Zheng, Paul D.P. Pharoah, Alison M. Dunning, Peter Kraft, Immaculata De Vivo, Ian Tomlinson, Douglas F. Easton, Amanda B. Spurdle, Deborah J. Thompson

Research output: Contribution to journal › Article

20 Scopus citations

Abstract

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.

Original language	English (US)
Article number	3166
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-05427-7
State	Published - Dec 1 2018

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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O’Mara, T. A., Glubb, D. M., Amant, F., Annibali, D., Ashton, K., Attia, J., Auer, P. L., Beckmann, M. W., Black, A., Bolla, M. K., Brauch, H., Brenner, H., Brinton, L., Buchanan, D. D., Burwinkel, B., Chang-Claude, J., Chanock, S. J., Chen, C., Chen, M. M., ... Thompson, D. J. (2018). Identification of nine new susceptibility loci for endometrial cancer. Nature communications, 9(1), [3166]. https://doi.org/10.1038/s41467-018-05427-7

Identification of nine new susceptibility loci for endometrial cancer. / O’Mara, Tracy A.; Glubb, Dylan M.; Amant, Frederic; Annibali, Daniela; Ashton, Katie; Attia, John; Auer, Paul L.; Beckmann, Matthias W.; Black, Amanda; Bolla, Manjeet K.; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Buchanan, Daniel D.; Burwinkel, Barbara; Chang-Claude, Jenny; Chanock, Stephen J.; Chen, Chu; Chen, Maxine M.; Cheng, Timothy H.T.; Clarke, Christine L.; Clendenning, Mark; Cook, Linda S.; Couch, Fergus J.; Cox, Angela; Crous-Bous, Marta; Czene, Kamila; Day, Felix; Dennis, Joe; Depreeuw, Jeroen; Doherty, Jennifer Anne; Dörk, Thilo; Dowdy, Sean C.; Dürst, Matthias; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Friedenreich, Christine M.; Fritschi, Lin; Fung, Jenny; García-Closas, Montserrat; Gaudet, Mia M.; Giles, Graham G.; Goode, Ellen L.; Gorman, Maggie; Haiman, Christopher A.; Hall, Per; Hankison, Susan E.; Healey, Catherine S.; Hein, Alexander; Hillemanns, Peter; Hodgson, Shirley; Hoivik, Erling A.; Holliday, Elizabeth G.; Hopper, John L.; Hunter, David J.; Jones, Angela; Krakstad, Camilla; Kristensen, Vessela N.; Lambrechts, Diether; Marchand, Loic Le; Liang, Xiaolin; Lindblom, Annika; Lissowska, Jolanta; Long, Jirong; Lu, Lingeng; Magliocco, Anthony M.; Martin, Lynn; McEvoy, Mark; Meindl, Alfons; Michailidou, Kyriaki; Milne, Roger L.; Mints, Miriam; Montgomery, Grant W.; Nassir, Rami; Olsson, Håkan; Orlow, Irene; Otton, Geoffrey; Palles, Claire; Perry, John R.B.; Peto, Julian; Pooler, Loreall; Prescott, Jennifer; Proietto, Tony; Rebbeck, Timothy R.; Risch, Harvey A.; Rogers, Peter A.W.; Rübner, Matthias; Runnebaum, Ingo; Sacerdote, Carlotta; Sarto, Gloria E.; Schumacher, Fredrick; Scott, Rodney J.; Setiawan, V. Wendy; Shah, Mitul; Sheng, Xin; Shu, Xiao Ou; Southey, Melissa C.; Swerdlow, Anthony J.; Tham, Emma; Trovik, Jone; Turman, Constance; Tyrer, Jonathan P.; Vachon, Celine; VanDen Berg, David; Vanderstichele, Adriaan; Wang, Zhaoming; Webb, Penelope M.; Wentzensen, Nicolas; Werner, Henrica M.J.; Winham, Stacey J.; Wolk, Alicja; Xia, Lucy; Xiang, Yong Bing; Yang, Hannah P.; Yu, Herbert; Zheng, Wei; Pharoah, Paul D.P.; Dunning, Alison M.; Kraft, Peter; De Vivo, Immaculata; Tomlinson, Ian; Easton, Douglas F.; Spurdle, Amanda B.; Thompson, Deborah J.

In: Nature communications, Vol. 9, No. 1, 3166, 01.12.2018.

Research output: Contribution to journal › Article

O’Mara, TA, Glubb, DM, Amant, F, Annibali, D, Ashton, K, Attia, J, Auer, PL, Beckmann, MW, Black, A, Bolla, MK, Brauch, H, Brenner, H, Brinton, L, Buchanan, DD, Burwinkel, B, Chang-Claude, J, Chanock, SJ, Chen, C, Chen, MM, Cheng, THT, Clarke, CL, Clendenning, M, Cook, LS, Couch, FJ, Cox, A, Crous-Bous, M, Czene, K, Day, F, Dennis, J, Depreeuw, J, Doherty, JA, Dörk, T, Dowdy, SC, Dürst, M, Ekici, AB, Fasching, PA, Fridley, BL, Friedenreich, CM, Fritschi, L, Fung, J, García-Closas, M, Gaudet, MM, Giles, GG, Goode, EL, Gorman, M, Haiman, CA, Hall, P, Hankison, SE, Healey, CS, Hein, A, Hillemanns, P, Hodgson, S, Hoivik, EA, Holliday, EG, Hopper, JL, Hunter, DJ, Jones, A, Krakstad, C, Kristensen, VN, Lambrechts, D, Marchand, LL, Liang, X, Lindblom, A, Lissowska, J, Long, J, Lu, L, Magliocco, AM, Martin, L, McEvoy, M, Meindl, A, Michailidou, K, Milne, RL, Mints, M, Montgomery, GW, Nassir, R, Olsson, H, Orlow, I, Otton, G, Palles, C, Perry, JRB, Peto, J, Pooler, L, Prescott, J, Proietto, T, Rebbeck, TR, Risch, HA, Rogers, PAW, Rübner, M, Runnebaum, I, Sacerdote, C, Sarto, GE, Schumacher, F, Scott, RJ, Setiawan, VW, Shah, M, Sheng, X, Shu, XO, Southey, MC, Swerdlow, AJ, Tham, E, Trovik, J, Turman, C, Tyrer, JP, Vachon, C, VanDen Berg, D, Vanderstichele, A, Wang, Z, Webb, PM, Wentzensen, N, Werner, HMJ, Winham, SJ, Wolk, A, Xia, L, Xiang, YB, Yang, HP, Yu, H, Zheng, W, Pharoah, PDP, Dunning, AM, Kraft, P, De Vivo, I, Tomlinson, I, Easton, DF, Spurdle, AB & Thompson, DJ 2018, 'Identification of nine new susceptibility loci for endometrial cancer', Nature communications, vol. 9, no. 1, 3166. https://doi.org/10.1038/s41467-018-05427-7

O’Mara, Tracy A. ; Glubb, Dylan M. ; Amant, Frederic ; Annibali, Daniela ; Ashton, Katie ; Attia, John ; Auer, Paul L. ; Beckmann, Matthias W. ; Black, Amanda ; Bolla, Manjeet K. ; Brauch, Hiltrud ; Brenner, Hermann ; Brinton, Louise ; Buchanan, Daniel D. ; Burwinkel, Barbara ; Chang-Claude, Jenny ; Chanock, Stephen J. ; Chen, Chu ; Chen, Maxine M. ; Cheng, Timothy H.T. ; Clarke, Christine L. ; Clendenning, Mark ; Cook, Linda S. ; Couch, Fergus J. ; Cox, Angela ; Crous-Bous, Marta ; Czene, Kamila ; Day, Felix ; Dennis, Joe ; Depreeuw, Jeroen ; Doherty, Jennifer Anne ; Dörk, Thilo ; Dowdy, Sean C. ; Dürst, Matthias ; Ekici, Arif B. ; Fasching, Peter A. ; Fridley, Brooke L. ; Friedenreich, Christine M. ; Fritschi, Lin ; Fung, Jenny ; García-Closas, Montserrat ; Gaudet, Mia M. ; Giles, Graham G. ; Goode, Ellen L. ; Gorman, Maggie ; Haiman, Christopher A. ; Hall, Per ; Hankison, Susan E. ; Healey, Catherine S. ; Hein, Alexander ; Hillemanns, Peter ; Hodgson, Shirley ; Hoivik, Erling A. ; Holliday, Elizabeth G. ; Hopper, John L. ; Hunter, David J. ; Jones, Angela ; Krakstad, Camilla ; Kristensen, Vessela N. ; Lambrechts, Diether ; Marchand, Loic Le ; Liang, Xiaolin ; Lindblom, Annika ; Lissowska, Jolanta ; Long, Jirong ; Lu, Lingeng ; Magliocco, Anthony M. ; Martin, Lynn ; McEvoy, Mark ; Meindl, Alfons ; Michailidou, Kyriaki ; Milne, Roger L. ; Mints, Miriam ; Montgomery, Grant W. ; Nassir, Rami ; Olsson, Håkan ; Orlow, Irene ; Otton, Geoffrey ; Palles, Claire ; Perry, John R.B. ; Peto, Julian ; Pooler, Loreall ; Prescott, Jennifer ; Proietto, Tony ; Rebbeck, Timothy R. ; Risch, Harvey A. ; Rogers, Peter A.W. ; Rübner, Matthias ; Runnebaum, Ingo ; Sacerdote, Carlotta ; Sarto, Gloria E. ; Schumacher, Fredrick ; Scott, Rodney J. ; Setiawan, V. Wendy ; Shah, Mitul ; Sheng, Xin ; Shu, Xiao Ou ; Southey, Melissa C. ; Swerdlow, Anthony J. ; Tham, Emma ; Trovik, Jone ; Turman, Constance ; Tyrer, Jonathan P. ; Vachon, Celine ; VanDen Berg, David ; Vanderstichele, Adriaan ; Wang, Zhaoming ; Webb, Penelope M. ; Wentzensen, Nicolas ; Werner, Henrica M.J. ; Winham, Stacey J. ; Wolk, Alicja ; Xia, Lucy ; Xiang, Yong Bing ; Yang, Hannah P. ; Yu, Herbert ; Zheng, Wei ; Pharoah, Paul D.P. ; Dunning, Alison M. ; Kraft, Peter ; De Vivo, Immaculata ; Tomlinson, Ian ; Easton, Douglas F. ; Spurdle, Amanda B. ; Thompson, Deborah J. / Identification of nine new susceptibility loci for endometrial cancer. In: Nature communications. 2018 ; Vol. 9, No. 1.

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title = "Identification of nine new susceptibility loci for endometrial cancer",

abstract = "Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.",

author = "O{\textquoteright}Mara, {Tracy A.} and Glubb, {Dylan M.} and Frederic Amant and Daniela Annibali and Katie Ashton and John Attia and Auer, {Paul L.} and Beckmann, {Matthias W.} and Amanda Black and Bolla, {Manjeet K.} and Hiltrud Brauch and Hermann Brenner and Louise Brinton and Buchanan, {Daniel D.} and Barbara Burwinkel and Jenny Chang-Claude and Chanock, {Stephen J.} and Chu Chen and Chen, {Maxine M.} and Cheng, {Timothy H.T.} and Clarke, {Christine L.} and Mark Clendenning and Cook, {Linda S.} and Couch, {Fergus J.} and Angela Cox and Marta Crous-Bous and Kamila Czene and Felix Day and Joe Dennis and Jeroen Depreeuw and Doherty, {Jennifer Anne} and Thilo D{\"o}rk and Dowdy, {Sean C.} and Matthias D{\"u}rst and Ekici, {Arif B.} and Fasching, {Peter A.} and Fridley, {Brooke L.} and Friedenreich, {Christine M.} and Lin Fritschi and Jenny Fung and Montserrat Garc{\'i}a-Closas and Gaudet, {Mia M.} and Giles, {Graham G.} and Goode, {Ellen L.} and Maggie Gorman and Haiman, {Christopher A.} and Per Hall and Hankison, {Susan E.} and Healey, {Catherine S.} and Alexander Hein and Peter Hillemanns and Shirley Hodgson and Hoivik, {Erling A.} and Holliday, {Elizabeth G.} and Hopper, {John L.} and Hunter, {David J.} and Angela Jones and Camilla Krakstad and Kristensen, {Vessela N.} and Diether Lambrechts and Marchand, {Loic Le} and Xiaolin Liang and Annika Lindblom and Jolanta Lissowska and Jirong Long and Lingeng Lu and Magliocco, {Anthony M.} and Lynn Martin and Mark McEvoy and Alfons Meindl and Kyriaki Michailidou and Milne, {Roger L.} and Miriam Mints and Montgomery, {Grant W.} and Rami Nassir and H{\aa}kan Olsson and Irene Orlow and Geoffrey Otton and Claire Palles and Perry, {John R.B.} and Julian Peto and Loreall Pooler and Jennifer Prescott and Tony Proietto and Rebbeck, {Timothy R.} and Risch, {Harvey A.} and Rogers, {Peter A.W.} and Matthias R{\"u}bner and Ingo Runnebaum and Carlotta Sacerdote and Sarto, {Gloria E.} and Fredrick Schumacher and Scott, {Rodney J.} and Setiawan, {V. Wendy} and Mitul Shah and Xin Sheng and Shu, {Xiao Ou} and Southey, {Melissa C.} and Swerdlow, {Anthony J.} and Emma Tham and Jone Trovik and Constance Turman and Tyrer, {Jonathan P.} and Celine Vachon and {VanDen Berg}, David and Adriaan Vanderstichele and Zhaoming Wang and Webb, {Penelope M.} and Nicolas Wentzensen and Werner, {Henrica M.J.} and Winham, {Stacey J.} and Alicja Wolk and Lucy Xia and Xiang, {Yong Bing} and Yang, {Hannah P.} and Herbert Yu and Wei Zheng and Pharoah, {Paul D.P.} and Dunning, {Alison M.} and Peter Kraft and {De Vivo}, Immaculata and Ian Tomlinson and Easton, {Douglas F.} and Spurdle, {Amanda B.} and Thompson, {Deborah J.}",

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T1 - Identification of nine new susceptibility loci for endometrial cancer

AU - O’Mara, Tracy A.

AU - Glubb, Dylan M.

AU - Amant, Frederic

AU - Annibali, Daniela

AU - Ashton, Katie

AU - Attia, John

AU - Auer, Paul L.

AU - Beckmann, Matthias W.

AU - Black, Amanda

AU - Bolla, Manjeet K.

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Brinton, Louise

AU - Buchanan, Daniel D.

AU - Burwinkel, Barbara

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J.

AU - Chen, Chu

AU - Chen, Maxine M.

AU - Cheng, Timothy H.T.

AU - Clarke, Christine L.

AU - Clendenning, Mark

AU - Cook, Linda S.

AU - Couch, Fergus J.

AU - Cox, Angela

AU - Crous-Bous, Marta

AU - Czene, Kamila

AU - Day, Felix

AU - Dennis, Joe

AU - Depreeuw, Jeroen

AU - Doherty, Jennifer Anne

AU - Dörk, Thilo

AU - Dowdy, Sean C.

AU - Dürst, Matthias

AU - Ekici, Arif B.

AU - Fasching, Peter A.

AU - Fridley, Brooke L.

AU - Friedenreich, Christine M.

AU - Fritschi, Lin

AU - Fung, Jenny

AU - García-Closas, Montserrat

AU - Gaudet, Mia M.

AU - Giles, Graham G.

AU - Goode, Ellen L.

AU - Gorman, Maggie

AU - Haiman, Christopher A.

AU - Hall, Per

AU - Hankison, Susan E.

AU - Healey, Catherine S.

AU - Hein, Alexander

AU - Hillemanns, Peter

AU - Hodgson, Shirley

AU - Hoivik, Erling A.

AU - Holliday, Elizabeth G.

AU - Hopper, John L.

AU - Hunter, David J.

AU - Jones, Angela

AU - Krakstad, Camilla

AU - Kristensen, Vessela N.

AU - Lambrechts, Diether

AU - Marchand, Loic Le

AU - Liang, Xiaolin

AU - Lindblom, Annika

AU - Lissowska, Jolanta

AU - Long, Jirong

AU - Lu, Lingeng

AU - Magliocco, Anthony M.

AU - Martin, Lynn

AU - McEvoy, Mark

AU - Meindl, Alfons

AU - Michailidou, Kyriaki

AU - Milne, Roger L.

AU - Mints, Miriam

AU - Montgomery, Grant W.

AU - Nassir, Rami

AU - Olsson, Håkan

AU - Orlow, Irene

AU - Otton, Geoffrey

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AU - Prescott, Jennifer

AU - Proietto, Tony

AU - Rebbeck, Timothy R.

AU - Risch, Harvey A.

AU - Rogers, Peter A.W.

AU - Rübner, Matthias

AU - Runnebaum, Ingo

AU - Sacerdote, Carlotta

AU - Sarto, Gloria E.

AU - Schumacher, Fredrick

AU - Scott, Rodney J.

AU - Setiawan, V. Wendy

AU - Shah, Mitul

AU - Sheng, Xin

AU - Shu, Xiao Ou

AU - Southey, Melissa C.

AU - Swerdlow, Anthony J.

AU - Tham, Emma

AU - Trovik, Jone

AU - Turman, Constance

AU - Tyrer, Jonathan P.

AU - Vachon, Celine

AU - VanDen Berg, David

AU - Vanderstichele, Adriaan

AU - Wang, Zhaoming

AU - Webb, Penelope M.

AU - Wentzensen, Nicolas

AU - Werner, Henrica M.J.

AU - Winham, Stacey J.

AU - Wolk, Alicja

AU - Xia, Lucy

AU - Xiang, Yong Bing

AU - Yang, Hannah P.

AU - Yu, Herbert

AU - Zheng, Wei

AU - Pharoah, Paul D.P.

AU - Dunning, Alison M.

AU - Kraft, Peter

AU - De Vivo, Immaculata

AU - Tomlinson, Ian

AU - Easton, Douglas F.

AU - Spurdle, Amanda B.

AU - Thompson, Deborah J.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.

AB - Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.

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