Five endometrial cancer risk loci identified through genome-wide association analysis
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Five endometrial cancer risk loci identified through genome-wide association analysis. / Cheng, Timothy H T; Thompson, Deborah J; O'Mara, Tracy A; Painter, Jodie N; Glubb, Dylan M; Flach, Susanne; Lewis, Annabelle; French, Juliet D; Freeman-Mills, Luke; Church, David; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Webb, Penelope M; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Henders, Anjali K; Martin, Nicholas G; Montgomery, Grant W; Nyholt, Dale R; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Dennis, Joe; Fasching, Peter A; Beckmann, Matthias W; Hein, Alexander; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo; Amant, Frederic; Schrauwen, Stefanie; Zhao, Hui; Lambrechts, Diether; Depreeuw, Jeroen; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone; Werner, Henrica M J; Ashton, Katie; Otton, Geoffrey; Proietto, Tony; Liu, Tao; Mints, Miriam; Tham, Emma; Li, Mulin Jun; Yip, Shun H; Wang, Junwen; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Dunlop, Malcolm; Houlston, Richard; Palles, Claire; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Cunningham, Julie M; Pharoah, Paul D P; Dunning, Alison M; Edwards, Stacey L; Easton, Douglas F; Tomlinson, Ian; Spurdle, Amanda B; National Study of Endometrial Cancer Genetics Group (NSECG).
in: NAT GENET, Jahrgang 48, Nr. 6, 06.2016, S. 667-74.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Five endometrial cancer risk loci identified through genome-wide association analysis
AU - Cheng, Timothy H T
AU - Thompson, Deborah J
AU - O'Mara, Tracy A
AU - Painter, Jodie N
AU - Glubb, Dylan M
AU - Flach, Susanne
AU - Lewis, Annabelle
AU - French, Juliet D
AU - Freeman-Mills, Luke
AU - Church, David
AU - Gorman, Maggie
AU - Martin, Lynn
AU - Hodgson, Shirley
AU - Webb, Penelope M
AU - Attia, John
AU - Holliday, Elizabeth G
AU - McEvoy, Mark
AU - Scott, Rodney J
AU - Henders, Anjali K
AU - Martin, Nicholas G
AU - Montgomery, Grant W
AU - Nyholt, Dale R
AU - Ahmed, Shahana
AU - Healey, Catherine S
AU - Shah, Mitul
AU - Dennis, Joe
AU - Fasching, Peter A
AU - Beckmann, Matthias W
AU - Hein, Alexander
AU - Ekici, Arif B
AU - Hall, Per
AU - Czene, Kamila
AU - Darabi, Hatef
AU - Li, Jingmei
AU - Dörk, Thilo
AU - Dürst, Matthias
AU - Hillemanns, Peter
AU - Runnebaum, Ingo
AU - Amant, Frederic
AU - Schrauwen, Stefanie
AU - Zhao, Hui
AU - Lambrechts, Diether
AU - Depreeuw, Jeroen
AU - Dowdy, Sean C
AU - Goode, Ellen L
AU - Fridley, Brooke L
AU - Winham, Stacey J
AU - Njølstad, Tormund S
AU - Salvesen, Helga B
AU - Trovik, Jone
AU - Werner, Henrica M J
AU - Ashton, Katie
AU - Otton, Geoffrey
AU - Proietto, Tony
AU - Liu, Tao
AU - Mints, Miriam
AU - Tham, Emma
AU - Li, Mulin Jun
AU - Yip, Shun H
AU - Wang, Junwen
AU - Bolla, Manjeet K
AU - Michailidou, Kyriaki
AU - Wang, Qin
AU - Tyrer, Jonathan P
AU - Dunlop, Malcolm
AU - Houlston, Richard
AU - Palles, Claire
AU - Hopper, John L
AU - Peto, Julian
AU - Swerdlow, Anthony J
AU - Burwinkel, Barbara
AU - Brenner, Hermann
AU - Meindl, Alfons
AU - Brauch, Hiltrud
AU - Lindblom, Annika
AU - Chang-Claude, Jenny
AU - Couch, Fergus J
AU - Giles, Graham G
AU - Kristensen, Vessela N
AU - Cox, Angela
AU - Cunningham, Julie M
AU - Pharoah, Paul D P
AU - Dunning, Alison M
AU - Edwards, Stacey L
AU - Easton, Douglas F
AU - Tomlinson, Ian
AU - Spurdle, Amanda B
AU - National Study of Endometrial Cancer Genetics Group (NSECG)
PY - 2016/6
Y1 - 2016/6
N2 - We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.
AB - We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.
U2 - 10.1038/ng.3562
DO - 10.1038/ng.3562
M3 - SCORING: Journal article
C2 - 27135401
VL - 48
SP - 667
EP - 674
JO - NAT GENET
JF - NAT GENET
SN - 1061-4036
IS - 6
ER -