Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers
BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. W...
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| Veröffentlicht in: | CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION 2021-01, Vol.30 (1), p.217-228 |
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| creator | Glubb, Dylan M Thompson, Deborah J Aben, Katja K.H Alsulimani, Ahmad Amant, Frederic Annibali, Daniela Attia, John Barricarte, Aurelio Beckmann, Matthias W Berchuck, Andrew Bermisheva, Marina Bernardini, Marcus Q Bischof, Katharina Bjorge, Line Bodelon, Clara Brand, Alison H Brenton, James D Brinton, Louise A Bruinsma, Fiona Buchanan, Daniel D Burghaus, Stefanie Butzow, Ralf Cai, Hui Carney, Michael E Chanock, Stephen J Chen, Chu Chen, Xiao Qing Chen, Zhihua Cook, Linda S Cunningham, Julie M De Vivo, Immaculata DeFazio, Anna Doherty, Jennifer A Dork, Thilo du Bois, Andreas Dunning, Alison M Durst, Matthias Edwards, Todd Edwards, Robert P Ekici, Arif B Ewing, Ailith Fasching, Peter A Ferguson, Sarah Flanagan, James M Fostira, Florentia Fountzilas, George Friedenreich, Christine M Gao, Bo Gaudet, Mia M Gawelko, Jan Gentry-Maharaj, Aleksandra Giles, Graham G Glasspool, Rosalind Goodman, Marc T Gronwald, Jacek Harris, Holly R Harter, Philipp Hein, Alexander Heitz, Florian Hildebrandt, Michelle A.T Hillemanns, Peter Hogdall, Estrid Hogdall, Claus K Holliday, Elizabeth G Huntsman, David G Huzarski, Tomasz Jakubowska, Anna Jensen, Allan Jones, Michael E Karlan, Beth Y Karnezis, Anthony Kelley, Joseph L Khusnutdinova, Elza Killeen, Jeffrey L Kjaer, Susanne K Klapdor, Rudiger Kobel, Martin Konopka, Bozena Konstantopoulou, Irene Kopperud, Reidun K Koti, Madhuri Kraft, Peter Kupryjanczyk, Jolanta Lambrechts, Diether Larson, Melissa C Le Marchand, Loic Lele, Shashikant Lester, Jenny Li, Andrew J Liang, Dong Liebrich, Clemens Lipworth, Loren Lissowska, Jolanta Lu, Lingeng Lu, Karen H Macciotta, Alessandra Mattiello, Amalia May, Taymaa McAlpine, Jessica N McGuire, Valerie |
| description | BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. METHODS: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. RESULTS: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (P Bonferroni < 2.4 × 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. CONCLUSIONS: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings. |
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Thompson, Deborah J ; Aben, Katja K.H ; Alsulimani, Ahmad ; Amant, Frederic ; Annibali, Daniela ; Attia, John ; Barricarte, Aurelio ; Beckmann, Matthias W ; Berchuck, Andrew ; Bermisheva, Marina ; Bernardini, Marcus Q ; Bischof, Katharina ; Bjorge, Line ; Bodelon, Clara ; Brand, Alison H ; Brenton, James D ; Brinton, Louise A ; Bruinsma, Fiona ; Buchanan, Daniel D ; Burghaus, Stefanie ; Butzow, Ralf ; Cai, Hui ; Carney, Michael E ; Chanock, Stephen J ; Chen, Chu ; Chen, Xiao Qing ; Chen, Zhihua ; Cook, Linda S ; Cunningham, Julie M ; De Vivo, Immaculata ; DeFazio, Anna ; Doherty, Jennifer A ; Dork, Thilo ; du Bois, Andreas ; Dunning, Alison M ; Durst, Matthias ; Edwards, Todd ; Edwards, Robert P ; Ekici, Arif B ; Ewing, Ailith ; Fasching, Peter A ; Ferguson, Sarah ; Flanagan, James M ; Fostira, Florentia ; Fountzilas, George ; Friedenreich, Christine M ; Gao, Bo ; Gaudet, Mia M ; Gawelko, Jan ; Gentry-Maharaj, Aleksandra ; Giles, Graham G ; Glasspool, Rosalind ; Goodman, Marc T ; Gronwald, Jacek ; Harris, Holly R ; Harter, Philipp ; Hein, Alexander ; Heitz, Florian ; Hildebrandt, Michelle A.T ; Hillemanns, Peter ; Hogdall, Estrid ; Hogdall, Claus K ; Holliday, Elizabeth G ; Huntsman, David G ; Huzarski, Tomasz ; Jakubowska, Anna ; Jensen, Allan ; Jones, Michael E ; Karlan, Beth Y ; Karnezis, Anthony ; Kelley, Joseph L ; Khusnutdinova, Elza ; Killeen, Jeffrey L ; Kjaer, Susanne K ; Klapdor, Rudiger ; Kobel, Martin ; Konopka, Bozena ; Konstantopoulou, Irene ; Kopperud, Reidun K ; Koti, Madhuri ; Kraft, Peter ; Kupryjanczyk, Jolanta ; Lambrechts, Diether ; Larson, Melissa C ; Le Marchand, Loic ; Lele, Shashikant ; Lester, Jenny ; Li, Andrew J ; Liang, Dong ; Liebrich, Clemens ; Lipworth, Loren ; Lissowska, Jolanta ; Lu, Lingeng ; Lu, Karen H ; Macciotta, Alessandra ; Mattiello, Amalia ; May, Taymaa ; McAlpine, Jessica N ; McGuire, Valerie</creator><creatorcontrib>Glubb, Dylan M ; Thompson, Deborah J ; Aben, Katja K.H ; Alsulimani, Ahmad ; Amant, Frederic ; Annibali, Daniela ; Attia, John ; Barricarte, Aurelio ; Beckmann, Matthias W ; Berchuck, Andrew ; Bermisheva, Marina ; Bernardini, Marcus Q ; Bischof, Katharina ; Bjorge, Line ; Bodelon, Clara ; Brand, Alison H ; Brenton, James D ; Brinton, Louise A ; Bruinsma, Fiona ; Buchanan, Daniel D ; Burghaus, Stefanie ; Butzow, Ralf ; Cai, Hui ; Carney, Michael E ; Chanock, Stephen J ; Chen, Chu ; Chen, Xiao Qing ; Chen, Zhihua ; Cook, Linda S ; Cunningham, Julie M ; De Vivo, Immaculata ; DeFazio, Anna ; Doherty, Jennifer A ; Dork, Thilo ; du Bois, Andreas ; Dunning, Alison M ; Durst, Matthias ; Edwards, Todd ; Edwards, Robert P ; Ekici, Arif B ; Ewing, Ailith ; Fasching, Peter A ; Ferguson, Sarah ; Flanagan, James M ; Fostira, Florentia ; Fountzilas, George ; Friedenreich, Christine M ; Gao, Bo ; Gaudet, Mia M ; Gawelko, Jan ; Gentry-Maharaj, Aleksandra ; Giles, Graham G ; Glasspool, Rosalind ; Goodman, Marc T ; Gronwald, Jacek ; Harris, Holly R ; Harter, Philipp ; Hein, Alexander ; Heitz, Florian ; Hildebrandt, Michelle A.T ; Hillemanns, Peter ; Hogdall, Estrid ; Hogdall, Claus K ; Holliday, Elizabeth G ; Huntsman, David G ; Huzarski, Tomasz ; Jakubowska, Anna ; Jensen, Allan ; Jones, Michael E ; Karlan, Beth Y ; Karnezis, Anthony ; Kelley, Joseph L ; Khusnutdinova, Elza ; Killeen, Jeffrey L ; Kjaer, Susanne K ; Klapdor, Rudiger ; Kobel, Martin ; Konopka, Bozena ; Konstantopoulou, Irene ; Kopperud, Reidun K ; Koti, Madhuri ; Kraft, Peter ; Kupryjanczyk, Jolanta ; Lambrechts, Diether ; Larson, Melissa C ; Le Marchand, Loic ; Lele, Shashikant ; Lester, Jenny ; Li, Andrew J ; Liang, Dong ; Liebrich, Clemens ; Lipworth, Loren ; Lissowska, Jolanta ; Lu, Lingeng ; Lu, Karen H ; Macciotta, Alessandra ; Mattiello, Amalia ; May, Taymaa ; McAlpine, Jessica N ; McGuire, Valerie</creatorcontrib><description>BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. METHODS: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. RESULTS: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (P Bonferroni < 2.4 × 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. CONCLUSIONS: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.</description><identifier>ISSN: 1055-9965</identifier><language>eng</language><publisher>AMER ASSOC CANCER RESEARCH</publisher><ispartof>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2021-01, Vol.30 (1), p.217-228</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,776,780,27839</link.rule.ids></links><search><creatorcontrib>Glubb, Dylan M</creatorcontrib><creatorcontrib>Thompson, Deborah J</creatorcontrib><creatorcontrib>Aben, Katja K.H</creatorcontrib><creatorcontrib>Alsulimani, Ahmad</creatorcontrib><creatorcontrib>Amant, Frederic</creatorcontrib><creatorcontrib>Annibali, Daniela</creatorcontrib><creatorcontrib>Attia, John</creatorcontrib><creatorcontrib>Barricarte, Aurelio</creatorcontrib><creatorcontrib>Beckmann, Matthias W</creatorcontrib><creatorcontrib>Berchuck, Andrew</creatorcontrib><creatorcontrib>Bermisheva, Marina</creatorcontrib><creatorcontrib>Bernardini, Marcus Q</creatorcontrib><creatorcontrib>Bischof, Katharina</creatorcontrib><creatorcontrib>Bjorge, Line</creatorcontrib><creatorcontrib>Bodelon, Clara</creatorcontrib><creatorcontrib>Brand, Alison H</creatorcontrib><creatorcontrib>Brenton, James D</creatorcontrib><creatorcontrib>Brinton, Louise A</creatorcontrib><creatorcontrib>Bruinsma, Fiona</creatorcontrib><creatorcontrib>Buchanan, Daniel D</creatorcontrib><creatorcontrib>Burghaus, Stefanie</creatorcontrib><creatorcontrib>Butzow, Ralf</creatorcontrib><creatorcontrib>Cai, Hui</creatorcontrib><creatorcontrib>Carney, Michael E</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Chen, Chu</creatorcontrib><creatorcontrib>Chen, Xiao Qing</creatorcontrib><creatorcontrib>Chen, Zhihua</creatorcontrib><creatorcontrib>Cook, Linda S</creatorcontrib><creatorcontrib>Cunningham, Julie M</creatorcontrib><creatorcontrib>De Vivo, Immaculata</creatorcontrib><creatorcontrib>DeFazio, Anna</creatorcontrib><creatorcontrib>Doherty, Jennifer A</creatorcontrib><creatorcontrib>Dork, Thilo</creatorcontrib><creatorcontrib>du Bois, Andreas</creatorcontrib><creatorcontrib>Dunning, Alison M</creatorcontrib><creatorcontrib>Durst, Matthias</creatorcontrib><creatorcontrib>Edwards, Todd</creatorcontrib><creatorcontrib>Edwards, Robert P</creatorcontrib><creatorcontrib>Ekici, Arif B</creatorcontrib><creatorcontrib>Ewing, Ailith</creatorcontrib><creatorcontrib>Fasching, Peter A</creatorcontrib><creatorcontrib>Ferguson, Sarah</creatorcontrib><creatorcontrib>Flanagan, James M</creatorcontrib><creatorcontrib>Fostira, Florentia</creatorcontrib><creatorcontrib>Fountzilas, George</creatorcontrib><creatorcontrib>Friedenreich, Christine M</creatorcontrib><creatorcontrib>Gao, Bo</creatorcontrib><creatorcontrib>Gaudet, Mia M</creatorcontrib><creatorcontrib>Gawelko, Jan</creatorcontrib><creatorcontrib>Gentry-Maharaj, Aleksandra</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Glasspool, Rosalind</creatorcontrib><creatorcontrib>Goodman, Marc T</creatorcontrib><creatorcontrib>Gronwald, Jacek</creatorcontrib><creatorcontrib>Harris, Holly R</creatorcontrib><creatorcontrib>Harter, Philipp</creatorcontrib><creatorcontrib>Hein, Alexander</creatorcontrib><creatorcontrib>Heitz, Florian</creatorcontrib><creatorcontrib>Hildebrandt, Michelle A.T</creatorcontrib><creatorcontrib>Hillemanns, Peter</creatorcontrib><creatorcontrib>Hogdall, Estrid</creatorcontrib><creatorcontrib>Hogdall, Claus K</creatorcontrib><creatorcontrib>Holliday, Elizabeth G</creatorcontrib><creatorcontrib>Huntsman, David G</creatorcontrib><creatorcontrib>Huzarski, Tomasz</creatorcontrib><creatorcontrib>Jakubowska, Anna</creatorcontrib><creatorcontrib>Jensen, Allan</creatorcontrib><creatorcontrib>Jones, Michael E</creatorcontrib><creatorcontrib>Karlan, Beth Y</creatorcontrib><creatorcontrib>Karnezis, Anthony</creatorcontrib><creatorcontrib>Kelley, Joseph L</creatorcontrib><creatorcontrib>Khusnutdinova, Elza</creatorcontrib><creatorcontrib>Killeen, Jeffrey L</creatorcontrib><creatorcontrib>Kjaer, Susanne K</creatorcontrib><creatorcontrib>Klapdor, Rudiger</creatorcontrib><creatorcontrib>Kobel, Martin</creatorcontrib><creatorcontrib>Konopka, Bozena</creatorcontrib><creatorcontrib>Konstantopoulou, Irene</creatorcontrib><creatorcontrib>Kopperud, Reidun K</creatorcontrib><creatorcontrib>Koti, Madhuri</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Kupryjanczyk, Jolanta</creatorcontrib><creatorcontrib>Lambrechts, Diether</creatorcontrib><creatorcontrib>Larson, Melissa C</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Lele, Shashikant</creatorcontrib><creatorcontrib>Lester, Jenny</creatorcontrib><creatorcontrib>Li, Andrew J</creatorcontrib><creatorcontrib>Liang, Dong</creatorcontrib><creatorcontrib>Liebrich, Clemens</creatorcontrib><creatorcontrib>Lipworth, Loren</creatorcontrib><creatorcontrib>Lissowska, Jolanta</creatorcontrib><creatorcontrib>Lu, Lingeng</creatorcontrib><creatorcontrib>Lu, Karen H</creatorcontrib><creatorcontrib>Macciotta, Alessandra</creatorcontrib><creatorcontrib>Mattiello, Amalia</creatorcontrib><creatorcontrib>May, Taymaa</creatorcontrib><creatorcontrib>McAlpine, Jessica N</creatorcontrib><creatorcontrib>McGuire, Valerie</creatorcontrib><title>Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers</title><title>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION</title><description>BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. METHODS: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. RESULTS: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (P Bonferroni < 2.4 × 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. CONCLUSIONS: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.</description><issn>1055-9965</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>FZOIL</sourceid><recordid>eNqVjcFOwkAQhvcgiYC8w9w8mCaFdhd61KaoJxI04dhsulMZqLukswV8Hl_UJYBnPU1m_m--_0b0x7GUUZYpeSsGzJs4jqeZlH3xnbeOOcq1rbCFZ7TuE6MVGYRHZleR9uQsvPnOfIGrobAmAL4l3cDlR1sDxY78GpvTdbHXIbXX9NWg9VQT8kmOnipYEm9hiR9BzL8taOAQHOcwFD25sJwdfCd6tW4YR5c5FPfz4j1_ibZdg90ebWl4pyssx5MklWo6y0ql0plKk_-QD38jS3_0yQ93hGrU</recordid><startdate>202101</startdate><enddate>202101</enddate><creator>Glubb, Dylan M</creator><creator>Thompson, Deborah J</creator><creator>Aben, Katja K.H</creator><creator>Alsulimani, Ahmad</creator><creator>Amant, Frederic</creator><creator>Annibali, Daniela</creator><creator>Attia, John</creator><creator>Barricarte, Aurelio</creator><creator>Beckmann, Matthias W</creator><creator>Berchuck, Andrew</creator><creator>Bermisheva, Marina</creator><creator>Bernardini, Marcus Q</creator><creator>Bischof, Katharina</creator><creator>Bjorge, Line</creator><creator>Bodelon, Clara</creator><creator>Brand, Alison H</creator><creator>Brenton, James D</creator><creator>Brinton, Louise A</creator><creator>Bruinsma, Fiona</creator><creator>Buchanan, Daniel D</creator><creator>Burghaus, Stefanie</creator><creator>Butzow, Ralf</creator><creator>Cai, Hui</creator><creator>Carney, Michael E</creator><creator>Chanock, Stephen J</creator><creator>Chen, Chu</creator><creator>Chen, Xiao Qing</creator><creator>Chen, Zhihua</creator><creator>Cook, Linda S</creator><creator>Cunningham, Julie M</creator><creator>De Vivo, Immaculata</creator><creator>DeFazio, Anna</creator><creator>Doherty, Jennifer A</creator><creator>Dork, Thilo</creator><creator>du Bois, Andreas</creator><creator>Dunning, Alison M</creator><creator>Durst, Matthias</creator><creator>Edwards, Todd</creator><creator>Edwards, Robert P</creator><creator>Ekici, Arif 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Alessandra</creator><creator>Mattiello, Amalia</creator><creator>May, Taymaa</creator><creator>McAlpine, Jessica N</creator><creator>McGuire, Valerie</creator><general>AMER ASSOC CANCER RESEARCH</general><scope>FZOIL</scope></search><sort><creationdate>202101</creationdate><title>Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers</title><author>Glubb, Dylan M ; Thompson, Deborah J ; Aben, Katja K.H ; Alsulimani, Ahmad ; Amant, Frederic ; Annibali, Daniela ; Attia, John ; Barricarte, Aurelio ; Beckmann, Matthias W ; Berchuck, Andrew ; Bermisheva, Marina ; Bernardini, Marcus Q ; Bischof, Katharina ; Bjorge, Line ; Bodelon, Clara ; Brand, Alison H ; Brenton, James D ; Brinton, Louise A ; Bruinsma, Fiona ; Buchanan, Daniel D ; Burghaus, Stefanie ; Butzow, Ralf ; Cai, Hui ; Carney, Michael E ; Chanock, Stephen J ; Chen, Chu ; Chen, Xiao Qing ; Chen, Zhihua ; Cook, Linda S ; Cunningham, Julie M ; De Vivo, Immaculata ; DeFazio, Anna ; Doherty, Jennifer A ; Dork, Thilo ; du Bois, Andreas ; Dunning, Alison M ; Durst, Matthias ; Edwards, Todd ; Edwards, Robert P ; Ekici, Arif B ; Ewing, Ailith ; Fasching, Peter A ; Ferguson, Sarah ; Flanagan, James M ; Fostira, Florentia ; Fountzilas, George ; Friedenreich, Christine M ; Gao, Bo ; Gaudet, Mia M ; Gawelko, Jan ; Gentry-Maharaj, Aleksandra ; Giles, Graham G ; Glasspool, Rosalind ; Goodman, Marc T ; Gronwald, Jacek ; Harris, Holly R ; Harter, Philipp ; Hein, Alexander ; Heitz, Florian ; Hildebrandt, Michelle A.T ; Hillemanns, Peter ; Hogdall, Estrid ; Hogdall, Claus K ; Holliday, Elizabeth G ; Huntsman, David G ; Huzarski, Tomasz ; Jakubowska, Anna ; Jensen, Allan ; Jones, Michael E ; Karlan, Beth Y ; Karnezis, Anthony ; Kelley, Joseph L ; Khusnutdinova, Elza ; Killeen, Jeffrey L ; Kjaer, Susanne K ; Klapdor, Rudiger ; Kobel, Martin ; Konopka, Bozena ; Konstantopoulou, Irene ; Kopperud, Reidun K ; Koti, Madhuri ; Kraft, Peter ; Kupryjanczyk, Jolanta ; Lambrechts, Diether ; Larson, Melissa C ; Le Marchand, Loic ; Lele, Shashikant ; Lester, Jenny ; Li, Andrew J ; Liang, Dong ; Liebrich, Clemens ; Lipworth, Loren ; Lissowska, Jolanta ; Lu, Lingeng ; Lu, Karen H ; Macciotta, Alessandra ; Mattiello, Amalia ; May, Taymaa ; McAlpine, Jessica N ; McGuire, Valerie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-kuleuven_dspace_123456789_6648643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Glubb, Dylan M</creatorcontrib><creatorcontrib>Thompson, Deborah J</creatorcontrib><creatorcontrib>Aben, Katja K.H</creatorcontrib><creatorcontrib>Alsulimani, Ahmad</creatorcontrib><creatorcontrib>Amant, Frederic</creatorcontrib><creatorcontrib>Annibali, Daniela</creatorcontrib><creatorcontrib>Attia, John</creatorcontrib><creatorcontrib>Barricarte, Aurelio</creatorcontrib><creatorcontrib>Beckmann, Matthias W</creatorcontrib><creatorcontrib>Berchuck, Andrew</creatorcontrib><creatorcontrib>Bermisheva, Marina</creatorcontrib><creatorcontrib>Bernardini, Marcus Q</creatorcontrib><creatorcontrib>Bischof, Katharina</creatorcontrib><creatorcontrib>Bjorge, Line</creatorcontrib><creatorcontrib>Bodelon, Clara</creatorcontrib><creatorcontrib>Brand, Alison H</creatorcontrib><creatorcontrib>Brenton, James D</creatorcontrib><creatorcontrib>Brinton, Louise A</creatorcontrib><creatorcontrib>Bruinsma, Fiona</creatorcontrib><creatorcontrib>Buchanan, Daniel D</creatorcontrib><creatorcontrib>Burghaus, Stefanie</creatorcontrib><creatorcontrib>Butzow, Ralf</creatorcontrib><creatorcontrib>Cai, Hui</creatorcontrib><creatorcontrib>Carney, Michael E</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Chen, Chu</creatorcontrib><creatorcontrib>Chen, Xiao Qing</creatorcontrib><creatorcontrib>Chen, Zhihua</creatorcontrib><creatorcontrib>Cook, Linda S</creatorcontrib><creatorcontrib>Cunningham, Julie M</creatorcontrib><creatorcontrib>De Vivo, Immaculata</creatorcontrib><creatorcontrib>DeFazio, Anna</creatorcontrib><creatorcontrib>Doherty, Jennifer A</creatorcontrib><creatorcontrib>Dork, Thilo</creatorcontrib><creatorcontrib>du Bois, Andreas</creatorcontrib><creatorcontrib>Dunning, Alison M</creatorcontrib><creatorcontrib>Durst, Matthias</creatorcontrib><creatorcontrib>Edwards, Todd</creatorcontrib><creatorcontrib>Edwards, Robert P</creatorcontrib><creatorcontrib>Ekici, Arif B</creatorcontrib><creatorcontrib>Ewing, Ailith</creatorcontrib><creatorcontrib>Fasching, Peter A</creatorcontrib><creatorcontrib>Ferguson, Sarah</creatorcontrib><creatorcontrib>Flanagan, James M</creatorcontrib><creatorcontrib>Fostira, Florentia</creatorcontrib><creatorcontrib>Fountzilas, George</creatorcontrib><creatorcontrib>Friedenreich, Christine M</creatorcontrib><creatorcontrib>Gao, Bo</creatorcontrib><creatorcontrib>Gaudet, Mia M</creatorcontrib><creatorcontrib>Gawelko, Jan</creatorcontrib><creatorcontrib>Gentry-Maharaj, Aleksandra</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Glasspool, Rosalind</creatorcontrib><creatorcontrib>Goodman, Marc T</creatorcontrib><creatorcontrib>Gronwald, Jacek</creatorcontrib><creatorcontrib>Harris, Holly R</creatorcontrib><creatorcontrib>Harter, Philipp</creatorcontrib><creatorcontrib>Hein, Alexander</creatorcontrib><creatorcontrib>Heitz, Florian</creatorcontrib><creatorcontrib>Hildebrandt, Michelle A.T</creatorcontrib><creatorcontrib>Hillemanns, Peter</creatorcontrib><creatorcontrib>Hogdall, Estrid</creatorcontrib><creatorcontrib>Hogdall, Claus K</creatorcontrib><creatorcontrib>Holliday, Elizabeth G</creatorcontrib><creatorcontrib>Huntsman, David G</creatorcontrib><creatorcontrib>Huzarski, Tomasz</creatorcontrib><creatorcontrib>Jakubowska, Anna</creatorcontrib><creatorcontrib>Jensen, Allan</creatorcontrib><creatorcontrib>Jones, Michael E</creatorcontrib><creatorcontrib>Karlan, Beth Y</creatorcontrib><creatorcontrib>Karnezis, Anthony</creatorcontrib><creatorcontrib>Kelley, Joseph L</creatorcontrib><creatorcontrib>Khusnutdinova, Elza</creatorcontrib><creatorcontrib>Killeen, Jeffrey L</creatorcontrib><creatorcontrib>Kjaer, Susanne K</creatorcontrib><creatorcontrib>Klapdor, Rudiger</creatorcontrib><creatorcontrib>Kobel, Martin</creatorcontrib><creatorcontrib>Konopka, Bozena</creatorcontrib><creatorcontrib>Konstantopoulou, Irene</creatorcontrib><creatorcontrib>Kopperud, Reidun K</creatorcontrib><creatorcontrib>Koti, Madhuri</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Kupryjanczyk, Jolanta</creatorcontrib><creatorcontrib>Lambrechts, Diether</creatorcontrib><creatorcontrib>Larson, Melissa C</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Lele, Shashikant</creatorcontrib><creatorcontrib>Lester, Jenny</creatorcontrib><creatorcontrib>Li, Andrew J</creatorcontrib><creatorcontrib>Liang, Dong</creatorcontrib><creatorcontrib>Liebrich, Clemens</creatorcontrib><creatorcontrib>Lipworth, Loren</creatorcontrib><creatorcontrib>Lissowska, Jolanta</creatorcontrib><creatorcontrib>Lu, Lingeng</creatorcontrib><creatorcontrib>Lu, Karen H</creatorcontrib><creatorcontrib>Macciotta, Alessandra</creatorcontrib><creatorcontrib>Mattiello, Amalia</creatorcontrib><creatorcontrib>May, Taymaa</creatorcontrib><creatorcontrib>McAlpine, Jessica N</creatorcontrib><creatorcontrib>McGuire, Valerie</creatorcontrib><collection>Lirias (KU Leuven Association)</collection><jtitle>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Glubb, Dylan M</au><au>Thompson, Deborah J</au><au>Aben, Katja K.H</au><au>Alsulimani, Ahmad</au><au>Amant, Frederic</au><au>Annibali, Daniela</au><au>Attia, John</au><au>Barricarte, Aurelio</au><au>Beckmann, Matthias W</au><au>Berchuck, Andrew</au><au>Bermisheva, Marina</au><au>Bernardini, Marcus Q</au><au>Bischof, Katharina</au><au>Bjorge, Line</au><au>Bodelon, Clara</au><au>Brand, Alison H</au><au>Brenton, James D</au><au>Brinton, Louise A</au><au>Bruinsma, Fiona</au><au>Buchanan, Daniel D</au><au>Burghaus, Stefanie</au><au>Butzow, Ralf</au><au>Cai, Hui</au><au>Carney, Michael E</au><au>Chanock, Stephen J</au><au>Chen, Chu</au><au>Chen, Xiao Qing</au><au>Chen, Zhihua</au><au>Cook, Linda S</au><au>Cunningham, Julie M</au><au>De Vivo, Immaculata</au><au>DeFazio, Anna</au><au>Doherty, Jennifer A</au><au>Dork, Thilo</au><au>du Bois, Andreas</au><au>Dunning, Alison M</au><au>Durst, Matthias</au><au>Edwards, Todd</au><au>Edwards, Robert P</au><au>Ekici, Arif B</au><au>Ewing, Ailith</au><au>Fasching, Peter A</au><au>Ferguson, Sarah</au><au>Flanagan, James M</au><au>Fostira, Florentia</au><au>Fountzilas, George</au><au>Friedenreich, Christine M</au><au>Gao, Bo</au><au>Gaudet, Mia M</au><au>Gawelko, Jan</au><au>Gentry-Maharaj, Aleksandra</au><au>Giles, Graham G</au><au>Glasspool, Rosalind</au><au>Goodman, Marc T</au><au>Gronwald, Jacek</au><au>Harris, Holly R</au><au>Harter, Philipp</au><au>Hein, Alexander</au><au>Heitz, Florian</au><au>Hildebrandt, Michelle A.T</au><au>Hillemanns, Peter</au><au>Hogdall, Estrid</au><au>Hogdall, Claus K</au><au>Holliday, Elizabeth G</au><au>Huntsman, David G</au><au>Huzarski, Tomasz</au><au>Jakubowska, Anna</au><au>Jensen, Allan</au><au>Jones, Michael E</au><au>Karlan, Beth Y</au><au>Karnezis, Anthony</au><au>Kelley, Joseph L</au><au>Khusnutdinova, Elza</au><au>Killeen, Jeffrey L</au><au>Kjaer, Susanne K</au><au>Klapdor, Rudiger</au><au>Kobel, Martin</au><au>Konopka, Bozena</au><au>Konstantopoulou, Irene</au><au>Kopperud, Reidun K</au><au>Koti, Madhuri</au><au>Kraft, Peter</au><au>Kupryjanczyk, Jolanta</au><au>Lambrechts, Diether</au><au>Larson, Melissa C</au><au>Le Marchand, Loic</au><au>Lele, Shashikant</au><au>Lester, Jenny</au><au>Li, Andrew J</au><au>Liang, Dong</au><au>Liebrich, Clemens</au><au>Lipworth, Loren</au><au>Lissowska, Jolanta</au><au>Lu, Lingeng</au><au>Lu, Karen H</au><au>Macciotta, Alessandra</au><au>Mattiello, Amalia</au><au>May, Taymaa</au><au>McAlpine, Jessica N</au><au>McGuire, Valerie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers</atitle><jtitle>CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION</jtitle><date>2021-01</date><risdate>2021</risdate><volume>30</volume><issue>1</issue><spage>217</spage><epage>228</epage><pages>217-228</pages><issn>1055-9965</issn><abstract>BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. METHODS: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. RESULTS: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10-5). We found seven loci associated with risk for both cancers (P Bonferroni < 2.4 × 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. CONCLUSIONS: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.</abstract><pub>AMER ASSOC CANCER RESEARCH</pub><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1055-9965 |
| ispartof | CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2021-01, Vol.30 (1), p.217-228 |
| issn | 1055-9965 |
| language | eng |
| recordid | cdi_kuleuven_dspace_123456789_664864 |
| source | Lirias (KU Leuven Association); American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| title | Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T05%3A11%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-kuleuven&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cross-Cancer%20Genome-Wide%20Association%20Study%20of%20Endometrial%20Cancer%20and%20Epithelial%20Ovarian%20Cancer%20Identifies%20Genetic%20Risk%20Regions%20Associated%20with%20Risk%20of%20Both%20Cancers&rft.jtitle=CANCER%20EPIDEMIOLOGY%20BIOMARKERS%20&%20PREVENTION&rft.au=Glubb,%20Dylan%20M&rft.date=2021-01&rft.volume=30&rft.issue=1&rft.spage=217&rft.epage=228&rft.pages=217-228&rft.issn=1055-9965&rft_id=info:doi/&rft_dat=%3Ckuleuven%3E123456789_664864%3C/kuleuven%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |