Germline variation at 8q24 and prostate cancer risk in men of European ancestry
Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to...
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| creator | Matejcic, Marco Saunders, Edward J Dadaev, Tokhir Brook, Mark N Wang, Kan Sheng, Xin Olama, Ali Amin Al Schumacher, Fredrick R Ingles, Sue A Govindasami, Koveela Benlloch, Sara Berndt, Sonja I Albanes, Demetrius Koutros, Stella Muir, Kenneth Stevens, Victoria L Gapstur, Susan M Tangen, Catherine M Batra, Jyotsna Clements, Judith Gronberg, Henrik Pashayan, Nora Schleutker, Johanna Wolk, Alicja West, Catharine Mucci, Lorelei Kraft, Peter Cancel-Tassin, Géraldine Sorensen, Karina D Maehle, Lovise Grindedal, Eli M Strom, Sara S Neal, David E Hamdy, Freddie C Donovan, Jenny L Travis, Ruth C Hamilton, Robert J Rosenstein, Barry Lu, Yong-Jie Giles, Graham G Kibel, Adam S Vega, Ana Bensen, Jeanette T Kogevinas, Manolis Penney, Kathryn L Park, Jong Y Stanford, Janet L Cybulski, Cezary Nordestgaard, Børge G Brenner, Hermann Maier, Christiane Kim, Jeri Teixeira, Manuel R Neuhausen, Susan L De Ruyck, Kim Razack, Azad Newcomb, Lisa F Lessel, Davor Kaneva, Radka Usmani, Nawaid Claessens, Frank Townsend, Paul A Gago-Dominguez, Manuela Roobol, Monique J Menegaux, Florence Khaw, Kay-Tee Cannon-Albright, Lisa A Pandha, Hardev Thibodeau, Stephen N Schaid, Daniel J PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium Wiklund, Fredrik Chanock, Stephen J Easton, Douglas F Eeles, Rosalind A Kote-Jarai, Zsofia Conti, David V Haiman, Christopher A |
| description | Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p |
| format | Article |
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Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10-15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><language>eng</language><publisher>Nature Research (part of Springer Nature)</publisher><ispartof>Nature Communications, 2018-11, Vol.9 (1)</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>314,315,776,780,27837</link.rule.ids></links><search><creatorcontrib>Matejcic, Marco</creatorcontrib><creatorcontrib>Saunders, Edward J</creatorcontrib><creatorcontrib>Dadaev, Tokhir</creatorcontrib><creatorcontrib>Brook, Mark N</creatorcontrib><creatorcontrib>Wang, Kan</creatorcontrib><creatorcontrib>Sheng, Xin</creatorcontrib><creatorcontrib>Olama, Ali Amin Al</creatorcontrib><creatorcontrib>Schumacher, Fredrick R</creatorcontrib><creatorcontrib>Ingles, Sue A</creatorcontrib><creatorcontrib>Govindasami, Koveela</creatorcontrib><creatorcontrib>Benlloch, Sara</creatorcontrib><creatorcontrib>Berndt, Sonja I</creatorcontrib><creatorcontrib>Albanes, Demetrius</creatorcontrib><creatorcontrib>Koutros, Stella</creatorcontrib><creatorcontrib>Muir, Kenneth</creatorcontrib><creatorcontrib>Stevens, Victoria L</creatorcontrib><creatorcontrib>Gapstur, Susan M</creatorcontrib><creatorcontrib>Tangen, Catherine M</creatorcontrib><creatorcontrib>Batra, Jyotsna</creatorcontrib><creatorcontrib>Clements, Judith</creatorcontrib><creatorcontrib>Gronberg, Henrik</creatorcontrib><creatorcontrib>Pashayan, Nora</creatorcontrib><creatorcontrib>Schleutker, Johanna</creatorcontrib><creatorcontrib>Wolk, Alicja</creatorcontrib><creatorcontrib>West, Catharine</creatorcontrib><creatorcontrib>Mucci, Lorelei</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Cancel-Tassin, Géraldine</creatorcontrib><creatorcontrib>Sorensen, Karina D</creatorcontrib><creatorcontrib>Maehle, Lovise</creatorcontrib><creatorcontrib>Grindedal, Eli M</creatorcontrib><creatorcontrib>Strom, Sara S</creatorcontrib><creatorcontrib>Neal, David E</creatorcontrib><creatorcontrib>Hamdy, Freddie C</creatorcontrib><creatorcontrib>Donovan, Jenny L</creatorcontrib><creatorcontrib>Travis, Ruth C</creatorcontrib><creatorcontrib>Hamilton, Robert J</creatorcontrib><creatorcontrib>Rosenstein, Barry</creatorcontrib><creatorcontrib>Lu, Yong-Jie</creatorcontrib><creatorcontrib>Giles, Graham G</creatorcontrib><creatorcontrib>Kibel, Adam S</creatorcontrib><creatorcontrib>Vega, Ana</creatorcontrib><creatorcontrib>Bensen, Jeanette T</creatorcontrib><creatorcontrib>Kogevinas, Manolis</creatorcontrib><creatorcontrib>Penney, Kathryn L</creatorcontrib><creatorcontrib>Park, Jong Y</creatorcontrib><creatorcontrib>Stanford, Janet L</creatorcontrib><creatorcontrib>Cybulski, Cezary</creatorcontrib><creatorcontrib>Nordestgaard, Børge G</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Maier, Christiane</creatorcontrib><creatorcontrib>Kim, Jeri</creatorcontrib><creatorcontrib>Teixeira, Manuel R</creatorcontrib><creatorcontrib>Neuhausen, Susan L</creatorcontrib><creatorcontrib>De Ruyck, Kim</creatorcontrib><creatorcontrib>Razack, Azad</creatorcontrib><creatorcontrib>Newcomb, Lisa F</creatorcontrib><creatorcontrib>Lessel, Davor</creatorcontrib><creatorcontrib>Kaneva, Radka</creatorcontrib><creatorcontrib>Usmani, Nawaid</creatorcontrib><creatorcontrib>Claessens, Frank</creatorcontrib><creatorcontrib>Townsend, Paul A</creatorcontrib><creatorcontrib>Gago-Dominguez, Manuela</creatorcontrib><creatorcontrib>Roobol, Monique J</creatorcontrib><creatorcontrib>Menegaux, Florence</creatorcontrib><creatorcontrib>Khaw, Kay-Tee</creatorcontrib><creatorcontrib>Cannon-Albright, Lisa A</creatorcontrib><creatorcontrib>Pandha, Hardev</creatorcontrib><creatorcontrib>Thibodeau, Stephen N</creatorcontrib><creatorcontrib>Schaid, Daniel J</creatorcontrib><creatorcontrib>PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium</creatorcontrib><creatorcontrib>Wiklund, Fredrik</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Eeles, Rosalind A</creatorcontrib><creatorcontrib>Kote-Jarai, Zsofia</creatorcontrib><creatorcontrib>Conti, David V</creatorcontrib><creatorcontrib>Haiman, Christopher A</creatorcontrib><title>Germline variation at 8q24 and prostate cancer risk in men of European ancestry</title><title>Nature Communications</title><description>Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10-15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.</description><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>FZOIL</sourceid><recordid>eNqViz0PgjAURRujiUT5D29zMCTQVj5mg7q5uJMXeCQVKNgWov9eBgdHvcu9yTl3wTweyiiIEi6WX3vNfGvv4RyRRamUHrueyXSt0gQTGoVO9RrQQfrgElBXMJjeOnQEJeqSDBhlG1AaOtLQ15CPph8I589MrTOvLVvV2FryP71hu1N-O16CZmxpnEgXlR2wpCLiQh7iJM2KWAiRSPGPuf_NLNzTiTfQAk5A</recordid><startdate>20181105</startdate><enddate>20181105</enddate><creator>Matejcic, Marco</creator><creator>Saunders, Edward J</creator><creator>Dadaev, Tokhir</creator><creator>Brook, Mark N</creator><creator>Wang, Kan</creator><creator>Sheng, Xin</creator><creator>Olama, Ali Amin Al</creator><creator>Schumacher, Fredrick R</creator><creator>Ingles, Sue A</creator><creator>Govindasami, 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A</creatorcontrib><creatorcontrib>Pandha, Hardev</creatorcontrib><creatorcontrib>Thibodeau, Stephen N</creatorcontrib><creatorcontrib>Schaid, Daniel J</creatorcontrib><creatorcontrib>PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium</creatorcontrib><creatorcontrib>Wiklund, Fredrik</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Easton, Douglas F</creatorcontrib><creatorcontrib>Eeles, Rosalind A</creatorcontrib><creatorcontrib>Kote-Jarai, Zsofia</creatorcontrib><creatorcontrib>Conti, David V</creatorcontrib><creatorcontrib>Haiman, Christopher A</creatorcontrib><collection>Lirias (KU Leuven Association)</collection><jtitle>Nature Communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matejcic, Marco</au><au>Saunders, Edward J</au><au>Dadaev, Tokhir</au><au>Brook, Mark N</au><au>Wang, Kan</au><au>Sheng, Xin</au><au>Olama, Ali Amin Al</au><au>Schumacher, Fredrick R</au><au>Ingles, Sue A</au><au>Govindasami, Koveela</au><au>Benlloch, Sara</au><au>Berndt, Sonja I</au><au>Albanes, Demetrius</au><au>Koutros, Stella</au><au>Muir, Kenneth</au><au>Stevens, Victoria L</au><au>Gapstur, Susan M</au><au>Tangen, Catherine M</au><au>Batra, Jyotsna</au><au>Clements, Judith</au><au>Gronberg, Henrik</au><au>Pashayan, Nora</au><au>Schleutker, Johanna</au><au>Wolk, Alicja</au><au>West, Catharine</au><au>Mucci, Lorelei</au><au>Kraft, Peter</au><au>Cancel-Tassin, Géraldine</au><au>Sorensen, Karina D</au><au>Maehle, Lovise</au><au>Grindedal, Eli M</au><au>Strom, Sara S</au><au>Neal, David E</au><au>Hamdy, Freddie C</au><au>Donovan, Jenny L</au><au>Travis, Ruth C</au><au>Hamilton, Robert J</au><au>Rosenstein, Barry</au><au>Lu, Yong-Jie</au><au>Giles, Graham G</au><au>Kibel, Adam S</au><au>Vega, Ana</au><au>Bensen, Jeanette T</au><au>Kogevinas, Manolis</au><au>Penney, Kathryn L</au><au>Park, Jong Y</au><au>Stanford, Janet L</au><au>Cybulski, Cezary</au><au>Nordestgaard, Børge G</au><au>Brenner, Hermann</au><au>Maier, Christiane</au><au>Kim, Jeri</au><au>Teixeira, Manuel R</au><au>Neuhausen, Susan L</au><au>De Ruyck, Kim</au><au>Razack, Azad</au><au>Newcomb, Lisa F</au><au>Lessel, Davor</au><au>Kaneva, Radka</au><au>Usmani, Nawaid</au><au>Claessens, Frank</au><au>Townsend, Paul A</au><au>Gago-Dominguez, Manuela</au><au>Roobol, Monique J</au><au>Menegaux, Florence</au><au>Khaw, Kay-Tee</au><au>Cannon-Albright, Lisa A</au><au>Pandha, Hardev</au><au>Thibodeau, Stephen N</au><au>Schaid, Daniel J</au><au>PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium</au><au>Wiklund, Fredrik</au><au>Chanock, Stephen J</au><au>Easton, Douglas F</au><au>Eeles, Rosalind A</au><au>Kote-Jarai, Zsofia</au><au>Conti, David V</au><au>Haiman, Christopher A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Germline variation at 8q24 and prostate cancer risk in men of European ancestry</atitle><jtitle>Nature Communications</jtitle><date>2018-11-05</date><risdate>2018</risdate><volume>9</volume><issue>1</issue><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10-15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.</abstract><pub>Nature Research (part of Springer Nature)</pub><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-1723 |
| ispartof | Nature Communications, 2018-11, Vol.9 (1) |
| issn | 2041-1723 2041-1723 |
| language | eng |
| recordid | cdi_kuleuven_dspace_123456789_633374 |
| source | Lirias (KU Leuven Association); Nature Free; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; Springer Nature OA Free Journals |
| title | Germline variation at 8q24 and prostate cancer risk in men of European ancestry |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T00%3A48%3A28IST&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=Germline%20variation%20at%208q24%20and%20prostate%20cancer%20risk%20in%20men%20of%20European%20ancestry&rft.jtitle=Nature%20Communications&rft.au=Matejcic,%20Marco&rft.date=2018-11-05&rft.volume=9&rft.issue=1&rft.issn=2041-1723&rft.eissn=2041-1723&rft_id=info:doi/&rft_dat=%3Ckuleuven%3E123456789_633374%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 |