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dc.contributor.author | Southey, Melissa C.![]() |
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dc.contributor.author | Goldgar, David E.![]() |
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dc.contributor.author | Winqvist, Robert![]() |
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dc.contributor.author | Pylkas, Katri![]() |
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dc.contributor.author | Couch, Fergus![]() |
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dc.contributor.author | Tischkowitz, Marc![]() |
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dc.contributor.author | Foulkes, William D.![]() |
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dc.contributor.author | Dennis, Joe![]() |
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dc.contributor.author | Michailidou, Kyriaki![]() |
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dc.contributor.author | Jansen van Rensburg, Elizabeth![]() |
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dc.contributor.author | Heikkinen, Tuomas![]() |
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dc.contributor.author | Nevanlinna, Heli![]() |
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dc.contributor.author | Hopper, John L.![]() |
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dc.contributor.author | Dork, Thilo![]() |
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dc.contributor.author | Claes, Kathleen B.M.![]() |
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dc.contributor.author | Reis-Filho, Jorge![]() |
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dc.contributor.author | Teo, Zhi Ling![]() |
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dc.contributor.author | Radice, Paolo![]() |
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dc.contributor.author | Catucci, Irene![]() |
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dc.contributor.author | Peterlongo, Paolo![]() |
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dc.contributor.author | Tsimiklis, Helen![]() |
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dc.contributor.author | Odefrey, Fabrice A.![]() |
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dc.contributor.author | Dowty, James G.![]() |
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dc.contributor.author | Schmidt, Marjanka K.![]() |
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dc.contributor.author | Broeks, Annegien![]() |
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dc.contributor.author | Hogervorst, Frans B.![]() |
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dc.contributor.author | Verhoef, Senno![]() |
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dc.contributor.author | Carpenter, Jane![]() |
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dc.contributor.author | Clarke, Christine![]() |
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dc.contributor.author | Scott, Rodney J.![]() |
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dc.contributor.author | Fasching, Peter A.![]() |
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dc.contributor.author | Haeberle, Lothar![]() |
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dc.contributor.author | Ekici, Arif B.![]() |
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dc.contributor.author | Beckmann, Matthias W.![]() |
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dc.contributor.author | Peto, Julian![]() |
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dc.contributor.author | Dos-Santos-Silva, Isabel![]() |
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dc.contributor.author | Fletcher, Olivia![]() |
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dc.contributor.author | Johnson, Nichola![]() |
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dc.contributor.author | Bolla, Manjeet K.![]() |
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dc.contributor.author | Sawyer, Elinor J.![]() |
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dc.contributor.author | Tomlinson, Ian![]() |
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dc.contributor.author | Kerin, Michael J.![]() |
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dc.contributor.author | Miller, Nicola![]() |
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dc.contributor.author | Marme, Federik![]() |
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dc.contributor.author | Burwinkel, Barbara![]() |
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dc.contributor.author | Yang, Rongxi![]() |
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dc.contributor.author | Guenel, Pascal![]() |
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dc.contributor.author | Truong, Therese![]() |
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dc.contributor.author | Menegaux, Florence![]() |
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dc.contributor.author | Sanchez, Marie![]() |
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dc.contributor.author | Bojesen, Stig E.![]() |
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dc.contributor.author | Nielsen, Sune F.![]() |
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dc.contributor.author | Flyger, Henrik![]() |
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dc.contributor.author | Benitez, Javier![]() |
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dc.contributor.author | Zamora, M. Pilar![]() |
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dc.contributor.author | Perez, Jose Ignacio Arias![]() |
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dc.contributor.author | Menendez, Primitiva![]() |
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dc.contributor.author | Anton-Culver, Hoda![]() |
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dc.contributor.author | Neuhausen, Susan![]() |
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dc.contributor.author | Ziogas, Argyrios![]() |
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dc.contributor.author | Clarke, Christina A.![]() |
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dc.contributor.author | Brenner, Hermann![]() |
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dc.contributor.author | Arndt, Volker![]() |
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dc.contributor.author | Stegmaier, Christa![]() |
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dc.contributor.author | Brauch, Hiltrud![]() |
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dc.contributor.author | Bruning, Thomas![]() |
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dc.contributor.author | Ko, Yon-Dschun![]() |
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dc.contributor.author | Muranen, Taru A.![]() |
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dc.contributor.author | Aittomaki, Kristiina![]() |
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dc.contributor.author | Blomqvist, Carl![]() |
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dc.contributor.author | Bogdanova, Natalia V.![]() |
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dc.contributor.author | Antonenkova, Natalia N.![]() |
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dc.contributor.author | Lindblom, Annika![]() |
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dc.contributor.author | Hartikainen, Jaana M.![]() |
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dc.contributor.author | Spurdle, Amanda B.![]() |
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dc.contributor.author | kConFab Investigators![]() |
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dc.contributor.author | Australian Ovarian Cancer Study Group![]() |
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dc.contributor.author | Wauters, Els![]() |
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dc.contributor.author | Weischer, Maren![]() |
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dc.contributor.author | Neal, David![]() |
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dc.contributor.author | Donovan, Jenny L.![]() |
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dc.contributor.author | Hamdy, Freddie C.![]() |
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dc.contributor.author | Park, Jong![]() |
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dc.contributor.author | Kaneva, Radka![]() |
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dc.contributor.author | Teixeira, Manuel R.![]() |
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dc.contributor.author | Kote-Jarai, Zsofia![]() |
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dc.date.accessioned | 2017-02-14T07:34:00Z | |
dc.date.available | 2017-02-14T07:34:00Z | |
dc.date.issued | 2016-09-05 | |
dc.description.abstract | BACKGROUND The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. METHODS We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. RESULTS For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. CONCLUSIONS This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important. | en_ZA |
dc.description.department | Genetics | en_ZA |
dc.description.librarian | am2017 | en_ZA |
dc.description.sponsorship | Funding for the iCOGS infrastructure came from: the European Community’s Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C5047/A8384, C5047/A15007, C5047/A10692, CRUK C8197/A10123), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (No. 1 U19 CA 148537—the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, the Ovarian Cancer Research Fund and Susan G Komen (WF). | en_ZA |
dc.description.uri | http://jmg.bmj.com | en_ZA |
dc.identifier.citation | Southey MC, Goldgar DE, Winqvist R, et al. PALB2, CHEK2 and ATM rare variants and cancer risk : data from COGS. Journal of Medical Genetics 2016;53:800–811. | en_ZA |
dc.identifier.issn | 2210-7762 | |
dc.identifier.other | 10.1136/jmedgenet-2016-103839 | |
dc.identifier.uri | http://hdl.handle.net/2263/59009 | |
dc.language.iso | en | en_ZA |
dc.publisher | Elsevier | en_ZA |
dc.rights | This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license. | en_ZA |
dc.subject | BRCA2 mutations | en_ZA |
dc.subject | Breast cancer risk | en_ZA |
dc.subject | Women | en_ZA |
dc.subject | Prostate cancer | en_ZA |
dc.title | PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS | en_ZA |
dc.type | Article | en_ZA |