GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer
Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They ident...
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| Veröffentlicht in: | Nature genetics 2013-04, Vol.45 (4), p.362-370 |
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| creator | Pharoah, Paul D P Ramus, Susan J Goode, Ellen L Fridley, Brooke L Tyrer, Jonathan P Shen, Howard Larson, Melissa C Tessier, Daniel C Vincent, Daniel Cunningham, Julie M Dennis, Joe Dicks, Ed Anton-Culver, Hoda Antonenkova, Natalia Baglietto, Laura Bandera, Elisa V Birrer, Michael J Bloom, Greg Bogdanova, Natalia Brenton, James D Brooks-Wilson, Angela Butzow, Ralf Campbell, Ian Carney, Michael E Chang-Claude, Jenny Chen, Y Anne Chow, Wong-Ho Coetzee, Gerhard Cook, Linda S Dürst, Matthias Eccles, Diana Edwards, Robert Ekici, Arif B Fenstermacher, David Garcia-Closas, Montserrat Gentry-Maharaj, Aleksandra Gjyshi, Anxhela Gore, Martin Guo, Qi Halle, Mari K Heitz, Florian Hillemanns, Peter Hoatlin, Maureen Høgdall, Estrid Høgdall, Claus K Hosono, Satoyo Jensen, Allan Karlan, Beth Y Kelemen, Linda E Krakstad, Camilla Kupryjanczyk, Jolanta Lambrechts, Diether Le, Nhu D Lee, Nathan Lee, Janet Lissowska, Jolanta Lubiński, Jan Lundvall, Lene Lurie, Galina Matsuo, Keitaro McGuire, Valerie McLaughlin, John R Menon, Usha Moysich, Kirsten B Ness, Roberta B Nevanlinna, Heli Nickels, Stefan Noushmehr, Houtan Orlow, Irene Pelttari, Liisa M Permuth-Wey, Jenny Pike, Malcolm C Poole, Elizabeth M Risch, Harvey A Rodriguez-Rodriguez, Lorna Rudolph, Anja Runnebaum, Ingo Severi, Gianluca Sieh, Weiva Terry, Kathryn L Tworoger, Shelley S Vierkant, Robert A Wentzensen, Nicolas Whittemore, Alice S Wik, Elisabeth Winterhoff, Boris Woo, Yin Ling Wu, Anna H Yang, Hannah P Zheng, Wei Zulkifli, Famida Goodman, Marc T Hall, Per Easton, Douglas F Pearce, Celeste L Chenevix-Trench, Georgia Iversen, Edwin Gayther, Simon A Schildkraut, Joellen M Sellers, Thomas A |
| description | Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.
Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652,
P
= 5.5 × 10
−9
) and 10p12 (rs1243180,
P
= 1.8 × 10
−8
) and another locus specific to the serous subtype at 17q12 (rs757210,
P
= 8.1 × 10
−10
). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated
CHMP4C
in the pathogenesis of ovarian cancer. |
| doi_str_mv | 10.1038/ng.2564 |
| format | Article |
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Ramus, Susan J ; Goode, Ellen L ; Fridley, Brooke L ; Tyrer, Jonathan P ; Shen, Howard ; Larson, Melissa C ; Tessier, Daniel C ; Vincent, Daniel ; Cunningham, Julie M ; Dennis, Joe ; Dicks, Ed ; Anton-Culver, Hoda ; Antonenkova, Natalia ; Baglietto, Laura ; Bandera, Elisa V ; Birrer, Michael J ; Bloom, Greg ; Bogdanova, Natalia ; Brenton, James D ; Brooks-Wilson, Angela ; Butzow, Ralf ; Campbell, Ian ; Carney, Michael E ; Chang-Claude, Jenny ; Chen, Y Anne ; Chow, Wong-Ho ; Coetzee, Gerhard ; Cook, Linda S ; Dürst, Matthias ; Eccles, Diana ; Edwards, Robert ; Ekici, Arif B ; Fenstermacher, David ; Garcia-Closas, Montserrat ; Gentry-Maharaj, Aleksandra ; Gjyshi, Anxhela ; Gore, Martin ; Guo, Qi ; Halle, Mari K ; Heitz, Florian ; Hillemanns, Peter ; Hoatlin, Maureen ; Høgdall, Estrid ; Høgdall, Claus K ; Hosono, Satoyo ; Jensen, Allan ; Karlan, Beth Y ; Kelemen, Linda E ; Krakstad, Camilla ; Kupryjanczyk, Jolanta ; Lambrechts, Diether ; Le, Nhu D ; Lee, Nathan ; Lee, Janet ; Lissowska, Jolanta ; Lubiński, Jan ; Lundvall, Lene ; Lurie, Galina ; Matsuo, Keitaro ; McGuire, Valerie ; McLaughlin, John R ; Menon, Usha ; Moysich, Kirsten B ; Ness, Roberta B ; Nevanlinna, Heli ; Nickels, Stefan ; Noushmehr, Houtan ; Orlow, Irene ; Pelttari, Liisa M ; Permuth-Wey, Jenny ; Pike, Malcolm C ; Poole, Elizabeth M ; Risch, Harvey A ; Rodriguez-Rodriguez, Lorna ; Rudolph, Anja ; Runnebaum, Ingo ; Severi, Gianluca ; Sieh, Weiva ; Terry, Kathryn L ; Tworoger, Shelley S ; Vierkant, Robert A ; Wentzensen, Nicolas ; Whittemore, Alice S ; Wik, Elisabeth ; Winterhoff, Boris ; Woo, Yin Ling ; Wu, Anna H ; Yang, Hannah P ; Zheng, Wei ; Zulkifli, Famida ; Goodman, Marc T ; Hall, Per ; Easton, Douglas F ; Pearce, Celeste L ; Chenevix-Trench, Georgia ; Iversen, Edwin ; Gayther, Simon A ; Schildkraut, Joellen M ; Sellers, Thomas A</creator><creatorcontrib>Pharoah, Paul D P ; Ramus, Susan J ; Goode, Ellen L ; Fridley, Brooke L ; Tyrer, Jonathan P ; Shen, Howard ; Larson, Melissa C ; Tessier, Daniel C ; Vincent, Daniel ; Cunningham, Julie M ; Dennis, Joe ; Dicks, Ed ; Anton-Culver, Hoda ; Antonenkova, Natalia ; Baglietto, Laura ; Bandera, Elisa V ; Birrer, Michael J ; Bloom, Greg ; Bogdanova, Natalia ; Brenton, James D ; Brooks-Wilson, Angela ; Butzow, Ralf ; Campbell, Ian ; Carney, Michael E ; Chang-Claude, Jenny ; Chen, Y Anne ; Chow, Wong-Ho ; Coetzee, Gerhard ; Cook, Linda S ; Dürst, Matthias ; Eccles, Diana ; Edwards, Robert ; Ekici, Arif B ; Fenstermacher, David ; Garcia-Closas, Montserrat ; Gentry-Maharaj, Aleksandra ; Gjyshi, Anxhela ; Gore, Martin ; Guo, Qi ; Halle, Mari K ; Heitz, Florian ; Hillemanns, Peter ; Hoatlin, Maureen ; Høgdall, Estrid ; Høgdall, Claus K ; Hosono, Satoyo ; Jensen, Allan ; Karlan, Beth Y ; Kelemen, Linda E ; Krakstad, Camilla ; Kupryjanczyk, Jolanta ; Lambrechts, Diether ; Le, Nhu D ; Lee, Nathan ; Lee, Janet ; Lissowska, Jolanta ; Lubiński, Jan ; Lundvall, Lene ; Lurie, Galina ; Matsuo, Keitaro ; McGuire, Valerie ; McLaughlin, John R ; Menon, Usha ; Moysich, Kirsten B ; Ness, Roberta B ; Nevanlinna, Heli ; Nickels, Stefan ; Noushmehr, Houtan ; Orlow, Irene ; Pelttari, Liisa M ; Permuth-Wey, Jenny ; Pike, Malcolm C ; Poole, Elizabeth M ; Risch, Harvey A ; Rodriguez-Rodriguez, Lorna ; Rudolph, Anja ; Runnebaum, Ingo ; Severi, Gianluca ; Sieh, Weiva ; Terry, Kathryn L ; Tworoger, Shelley S ; Vierkant, Robert A ; Wentzensen, Nicolas ; Whittemore, Alice S ; Wik, Elisabeth ; Winterhoff, Boris ; Woo, Yin Ling ; Wu, Anna H ; Yang, Hannah P ; Zheng, Wei ; Zulkifli, Famida ; Goodman, Marc T ; Hall, Per ; Easton, Douglas F ; Pearce, Celeste L ; Chenevix-Trench, Georgia ; Iversen, Edwin ; Gayther, Simon A ; Schildkraut, Joellen M ; Sellers, Thomas A ; Australian Ovarian Cancer Study Group ; Australian Cancer Study</creatorcontrib><description>Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.
Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652,
P
= 5.5 × 10
−9
) and 10p12 (rs1243180,
P
= 1.8 × 10
−8
) and another locus specific to the serous subtype at 17q12 (rs757210,
P
= 8.1 × 10
−10
). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated
CHMP4C
in the pathogenesis of ovarian cancer.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.2564</identifier><identifier>PMID: 23535730</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/208/205/2138 ; 631/208/68 ; 631/67/1517/1709 ; Agriculture ; Animal Genetics and Genomics ; Biomedicine ; Cancer Research ; Case-Control Studies ; Cooperative Behavior ; Cystadenocarcinoma, Serous - etiology ; Cystadenocarcinoma, Serous - pathology ; Female ; Gene Function ; Gene-Environment Interaction ; Genetic aspects ; Genetic Loci - genetics ; Genetic Predisposition to Disease ; Genetic susceptibility ; Genetics ; Genome-Wide Association Study ; Genotype ; Health aspects ; Human Genetics ; Humans ; Medical research ; Meta-Analysis as Topic ; Neoplasm Invasiveness ; Ovarian cancer ; Ovarian Neoplasms - etiology ; Ovarian Neoplasms - pathology ; Polymorphism, Single Nucleotide - genetics ; Risk Factors ; Single nucleotide polymorphisms ; Studies</subject><ispartof>Nature genetics, 2013-04, Vol.45 (4), p.362-370</ispartof><rights>Springer Nature America, Inc. 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c702t-1938ae5a76004443932e249da8068b5962dd9844b27a4fe2a8777638cd9b4af03</citedby><cites>FETCH-LOGICAL-c702t-1938ae5a76004443932e249da8068b5962dd9844b27a4fe2a8777638cd9b4af03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng.2564$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng.2564$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,550,776,780,881,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23535730$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:126492449$$DView record from Swedish 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L</creatorcontrib><creatorcontrib>Tworoger, Shelley S</creatorcontrib><creatorcontrib>Vierkant, Robert A</creatorcontrib><creatorcontrib>Wentzensen, Nicolas</creatorcontrib><creatorcontrib>Whittemore, Alice S</creatorcontrib><creatorcontrib>Wik, Elisabeth</creatorcontrib><creatorcontrib>Winterhoff, Boris</creatorcontrib><creatorcontrib>Woo, Yin Ling</creatorcontrib><creatorcontrib>Wu, Anna H</creatorcontrib><creatorcontrib>Yang, Hannah P</creatorcontrib><creatorcontrib>Zheng, Wei</creatorcontrib><creatorcontrib>Zulkifli, Famida</creatorcontrib><creatorcontrib>Goodman, Marc T</creatorcontrib><creatorcontrib>Hall, Per</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Pearce, Celeste L</creatorcontrib><creatorcontrib>Chenevix-Trench, Georgia</creatorcontrib><creatorcontrib>Iversen, Edwin</creatorcontrib><creatorcontrib>Gayther, Simon A</creatorcontrib><creatorcontrib>Schildkraut, Joellen M</creatorcontrib><creatorcontrib>Sellers, Thomas A</creatorcontrib><creatorcontrib>Australian Ovarian Cancer Study Group</creatorcontrib><creatorcontrib>Australian Cancer Study</creatorcontrib><title>GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.
Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652,
P
= 5.5 × 10
−9
) and 10p12 (rs1243180,
P
= 1.8 × 10
−8
) and another locus specific to the serous subtype at 17q12 (rs757210,
P
= 8.1 × 10
−10
). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated
CHMP4C
in the pathogenesis of ovarian cancer.</description><subject>631/208/205/2138</subject><subject>631/208/68</subject><subject>631/67/1517/1709</subject><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Case-Control Studies</subject><subject>Cooperative Behavior</subject><subject>Cystadenocarcinoma, Serous - etiology</subject><subject>Cystadenocarcinoma, Serous - pathology</subject><subject>Female</subject><subject>Gene Function</subject><subject>Gene-Environment Interaction</subject><subject>Genetic aspects</subject><subject>Genetic Loci - genetics</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic susceptibility</subject><subject>Genetics</subject><subject>Genome-Wide Association Study</subject><subject>Genotype</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Medical research</subject><subject>Meta-Analysis as Topic</subject><subject>Neoplasm Invasiveness</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - etiology</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Risk Factors</subject><subject>Single nucleotide 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meta-analysis and replication identifies three new susceptibility loci for ovarian cancer</title><author>Pharoah, Paul D P ; Ramus, Susan J ; Goode, Ellen L ; Fridley, Brooke L ; Tyrer, Jonathan P ; Shen, Howard ; Larson, Melissa C ; Tessier, Daniel C ; Vincent, Daniel ; Cunningham, Julie M ; Dennis, Joe ; Dicks, Ed ; Anton-Culver, Hoda ; Antonenkova, Natalia ; Baglietto, Laura ; Bandera, Elisa V ; Birrer, Michael J ; Bloom, Greg ; Bogdanova, Natalia ; Brenton, James D ; Brooks-Wilson, Angela ; Butzow, Ralf ; Campbell, Ian ; Carney, Michael E ; Chang-Claude, Jenny ; Chen, Y Anne ; Chow, Wong-Ho ; Coetzee, Gerhard ; Cook, Linda S ; Dürst, Matthias ; Eccles, Diana ; Edwards, Robert ; Ekici, Arif B ; Fenstermacher, David ; Garcia-Closas, Montserrat ; Gentry-Maharaj, Aleksandra ; Gjyshi, Anxhela ; Gore, Martin ; Guo, Qi ; Halle, Mari K ; Heitz, Florian ; Hillemanns, Peter ; Hoatlin, Maureen ; Høgdall, Estrid ; Høgdall, Claus K ; Hosono, Satoyo ; Jensen, Allan ; Karlan, Beth Y ; Kelemen, Linda E ; Krakstad, Camilla ; Kupryjanczyk, Jolanta ; Lambrechts, Diether ; Le, Nhu D ; Lee, Nathan ; Lee, Janet ; Lissowska, Jolanta ; Lubiński, Jan ; Lundvall, Lene ; Lurie, Galina ; Matsuo, Keitaro ; McGuire, Valerie ; McLaughlin, John R ; Menon, Usha ; Moysich, Kirsten B ; Ness, Roberta B ; Nevanlinna, Heli ; Nickels, Stefan ; Noushmehr, Houtan ; Orlow, Irene ; Pelttari, Liisa M ; Permuth-Wey, Jenny ; Pike, Malcolm C ; Poole, Elizabeth M ; Risch, Harvey A ; Rodriguez-Rodriguez, Lorna ; Rudolph, Anja ; Runnebaum, Ingo ; Severi, Gianluca ; Sieh, Weiva ; Terry, Kathryn L ; Tworoger, Shelley S ; Vierkant, Robert A ; Wentzensen, Nicolas ; Whittemore, Alice S ; Wik, Elisabeth ; Winterhoff, Boris ; Woo, Yin Ling ; Wu, Anna H ; Yang, Hannah P ; Zheng, Wei ; Zulkifli, Famida ; Goodman, Marc T ; Hall, Per ; Easton, Douglas F ; Pearce, Celeste L ; Chenevix-Trench, Georgia ; Iversen, Edwin ; Gayther, Simon A ; Schildkraut, Joellen M ; Sellers, Thomas 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Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pharoah, Paul D P</au><au>Ramus, Susan J</au><au>Goode, Ellen L</au><au>Fridley, Brooke L</au><au>Tyrer, Jonathan P</au><au>Shen, Howard</au><au>Larson, Melissa C</au><au>Tessier, Daniel C</au><au>Vincent, Daniel</au><au>Cunningham, Julie M</au><au>Dennis, Joe</au><au>Dicks, Ed</au><au>Anton-Culver, Hoda</au><au>Antonenkova, Natalia</au><au>Baglietto, Laura</au><au>Bandera, Elisa V</au><au>Birrer, Michael J</au><au>Bloom, Greg</au><au>Bogdanova, Natalia</au><au>Brenton, James D</au><au>Brooks-Wilson, Angela</au><au>Butzow, Ralf</au><au>Campbell, Ian</au><au>Carney, Michael E</au><au>Chang-Claude, Jenny</au><au>Chen, Y Anne</au><au>Chow, Wong-Ho</au><au>Coetzee, Gerhard</au><au>Cook, Linda S</au><au>Dürst, Matthias</au><au>Eccles, Diana</au><au>Edwards, Robert</au><au>Ekici, Arif B</au><au>Fenstermacher, David</au><au>Garcia-Closas, Montserrat</au><au>Gentry-Maharaj, Aleksandra</au><au>Gjyshi, Anxhela</au><au>Gore, Martin</au><au>Guo, Qi</au><au>Halle, Mari K</au><au>Heitz, Florian</au><au>Hillemanns, Peter</au><au>Hoatlin, Maureen</au><au>Høgdall, Estrid</au><au>Høgdall, Claus K</au><au>Hosono, Satoyo</au><au>Jensen, Allan</au><au>Karlan, Beth Y</au><au>Kelemen, Linda E</au><au>Krakstad, Camilla</au><au>Kupryjanczyk, Jolanta</au><au>Lambrechts, Diether</au><au>Le, Nhu D</au><au>Lee, Nathan</au><au>Lee, Janet</au><au>Lissowska, Jolanta</au><au>Lubiński, Jan</au><au>Lundvall, Lene</au><au>Lurie, Galina</au><au>Matsuo, Keitaro</au><au>McGuire, Valerie</au><au>McLaughlin, John R</au><au>Menon, Usha</au><au>Moysich, Kirsten B</au><au>Ness, Roberta B</au><au>Nevanlinna, Heli</au><au>Nickels, Stefan</au><au>Noushmehr, Houtan</au><au>Orlow, Irene</au><au>Pelttari, Liisa M</au><au>Permuth-Wey, Jenny</au><au>Pike, Malcolm C</au><au>Poole, Elizabeth M</au><au>Risch, Harvey A</au><au>Rodriguez-Rodriguez, Lorna</au><au>Rudolph, Anja</au><au>Runnebaum, Ingo</au><au>Severi, Gianluca</au><au>Sieh, Weiva</au><au>Terry, Kathryn L</au><au>Tworoger, Shelley S</au><au>Vierkant, Robert A</au><au>Wentzensen, Nicolas</au><au>Whittemore, Alice S</au><au>Wik, Elisabeth</au><au>Winterhoff, Boris</au><au>Woo, Yin Ling</au><au>Wu, Anna H</au><au>Yang, Hannah P</au><au>Zheng, Wei</au><au>Zulkifli, Famida</au><au>Goodman, Marc T</au><au>Hall, Per</au><au>Easton, Douglas F</au><au>Pearce, Celeste L</au><au>Chenevix-Trench, Georgia</au><au>Iversen, Edwin</au><au>Gayther, Simon A</au><au>Schildkraut, Joellen M</au><au>Sellers, Thomas A</au><aucorp>Australian Ovarian Cancer Study Group</aucorp><aucorp>Australian Cancer Study</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2013-04-01</date><risdate>2013</risdate><volume>45</volume><issue>4</issue><spage>362</spage><epage>370</epage><pages>362-370</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><abstract>Paul Pharoah, Joellen Schildkraut, Thomas Sellers and colleagues report a meta-analysis of genome-wide association studies for epithelial ovarian cancer and genotyping using the iCOGS array in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. They identify three new ovarian cancer susceptibility loci, including one specific to the serous subtype, and their integrated molecular analysis of genes and regulatory regions at these loci suggests disease mechanisms.
Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652,
P
= 5.5 × 10
−9
) and 10p12 (rs1243180,
P
= 1.8 × 10
−8
) and another locus specific to the serous subtype at 17q12 (rs757210,
P
= 8.1 × 10
−10
). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated
CHMP4C
in the pathogenesis of ovarian cancer.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>23535730</pmid><doi>10.1038/ng.2564</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2013-04, Vol.45 (4), p.362-370 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_530481 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Springer Nature - Connect here FIRST to enable access; SWEPUB Freely available online |
| subjects | 631/208/205/2138 631/208/68 631/67/1517/1709 Agriculture Animal Genetics and Genomics Biomedicine Cancer Research Case-Control Studies Cooperative Behavior Cystadenocarcinoma, Serous - etiology Cystadenocarcinoma, Serous - pathology Female Gene Function Gene-Environment Interaction Genetic aspects Genetic Loci - genetics Genetic Predisposition to Disease Genetic susceptibility Genetics Genome-Wide Association Study Genotype Health aspects Human Genetics Humans Medical research Meta-Analysis as Topic Neoplasm Invasiveness Ovarian cancer Ovarian Neoplasms - etiology Ovarian Neoplasms - pathology Polymorphism, Single Nucleotide - genetics Risk Factors Single nucleotide polymorphisms Studies |
| title | GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T18%3A08%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=GWAS%20meta-analysis%20and%20replication%20identifies%20three%20new%20susceptibility%20loci%20for%20ovarian%20cancer&rft.jtitle=Nature%20genetics&rft.au=Pharoah,%20Paul%20D%20P&rft.aucorp=Australian%20Ovarian%20Cancer%20Study%20Group&rft.date=2013-04-01&rft.volume=45&rft.issue=4&rft.spage=362&rft.epage=370&rft.pages=362-370&rft.issn=1061-4036&rft.eissn=1546-1718&rft_id=info:doi/10.1038/ng.2564&rft_dat=%3Cgale_swepu%3EA326350009%3C/gale_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1347618935&rft_id=info:pmid/23535730&rft_galeid=A326350009&rfr_iscdi=true |