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Five endometrial cancer risk loci identified through genome-wide association analysis
We conducted a meta-analysis of three endometrial cancer GWAS and two replication phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five novel risk loci of genome-wide significance at likely regulatory regions...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2016
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907351/ https://www.ncbi.nlm.nih.gov/pubmed/27135401 http://dx.doi.org/10.1038/ng.3562 |
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| author | Cheng, Timothy HT 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 MJ Ashton, Katie Otton, Geoffrey Proietto, Tony Liu, Tao Mints, Miriam Tham, Emma Consortium, CHIBCHA Jun Li, Mulin 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 |
| author_facet | Cheng, Timothy HT 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 MJ Ashton, Katie Otton, Geoffrey Proietto, Tony Liu, Tao Mints, Miriam Tham, Emma Consortium, CHIBCHA Jun Li, Mulin 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 |
| author_sort | Cheng, Timothy HT |
| collection | PubMed |
| description | We conducted a meta-analysis of three endometrial cancer GWAS and two replication phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five novel 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). A second independent 8q24.21 signal (rs17232730) was found. 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 endometrial cancer protective allele suppressed gene expression in vitro suggesting that regulation of KLF5 expression, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer. |
| format | Online Article Text |
| id | pubmed-4907351 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2016 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-49073512016-11-02 Five endometrial cancer risk loci identified through genome-wide association analysis Cheng, Timothy HT 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 MJ Ashton, Katie Otton, Geoffrey Proietto, Tony Liu, Tao Mints, Miriam Tham, Emma Consortium, CHIBCHA Jun Li, Mulin 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 Nat Genet Article We conducted a meta-analysis of three endometrial cancer GWAS and two replication phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five novel 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). A second independent 8q24.21 signal (rs17232730) was found. 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 endometrial cancer protective allele suppressed gene expression in vitro suggesting that regulation of KLF5 expression, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer. 2016-05-02 2016-06 /pmc/articles/PMC4907351/ /pubmed/27135401 http://dx.doi.org/10.1038/ng.3562 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Cheng, Timothy HT 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 MJ Ashton, Katie Otton, Geoffrey Proietto, Tony Liu, Tao Mints, Miriam Tham, Emma Consortium, CHIBCHA Jun Li, Mulin 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 Five endometrial cancer risk loci identified through genome-wide association analysis |
| title | Five endometrial cancer risk loci identified through genome-wide association analysis |
| title_full | Five endometrial cancer risk loci identified through genome-wide association analysis |
| title_fullStr | Five endometrial cancer risk loci identified through genome-wide association analysis |
| title_full_unstemmed | Five endometrial cancer risk loci identified through genome-wide association analysis |
| title_short | Five endometrial cancer risk loci identified through genome-wide association analysis |
| title_sort | five endometrial cancer risk loci identified through genome-wide association analysis |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907351/ https://www.ncbi.nlm.nih.gov/pubmed/27135401 http://dx.doi.org/10.1038/ng.3562 |
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