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 | |
| State | Published - Dec 1 2018 |
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ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
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 Christopher; 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 M; 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
}
TY - JOUR
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 Christopher
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
AU - Palles, Claire
AU - Perry, John R.B.
AU - Peto, Julian
AU - Pooler, Loreall
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 M
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.
UR - http://www.scopus.com/inward/record.url?scp=85051554034&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051554034&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-05427-7
DO - 10.1038/s41467-018-05427-7
M3 - Article
C2 - 30093612
AN - SCOPUS:85051554034
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3166
ER -