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Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

Gaudet, Mia M. (author)
Kirchhoff, Tomas (author)
Green, Todd (author)
show more...
Vijai, Joseph (author)
Korn, Joshua M. (author)
Guiducci, Candace (author)
Segre, Ayellet V. (author)
McGee, Kate (author)
McGuffog, Lesley (author)
Kartsonaki, Christiana (author)
Morrison, Jonathan (author)
Healey, Sue (author)
Sinilnikova, Olga M. (author)
Stoppa-Lyonnet, Dominique (author)
Mazoyer, Sylvie (author)
Gauthier-Villars, Marion (author)
Sobol, Hagay (author)
Longy, Michel (author)
Frenay, Marc (author)
Hogervorst, Frans B. L. (author)
Rookus, Matti A. (author)
Collee, J. Margriet (author)
Hoogerbrugge, Nicoline (author)
van Roozendaal, Kees E. P. (author)
Piedmonte, Marion (author)
Rubinstein, Wendy (author)
Nerenstone, Stacy (author)
Van Le, Linda (author)
Blank, Stephanie V. (author)
Caldes, Trinidad (author)
de la Hoya, Miguel (author)
Nevanlinna, Heli (author)
Aittomaki, Kristiina (author)
Lazaro, Conxi (author)
Blanco, Ignacio (author)
Arason, Adalgeir (author)
Johannsson, Oskar T. (author)
Barkardottir, Rosa B. (author)
Devilee, Peter (author)
Olopade, Olofunmilayo I. (author)
Neuhausen, Susan L. (author)
Wang, Xianshu (author)
Fredericksen, Zachary S. (author)
Peterlongo, Paolo (author)
Manoukian, Siranoush (author)
Barile, Monica (author)
Viel, Alessandra (author)
Radice, Paolo (author)
Phelan, Catherine M. (author)
Narod, Steven (author)
Rennert, Gad (author)
Lejbkowicz, Flavio (author)
Flugelman, Anath (author)
Andrulis, Irene L. (author)
Glendon, Gord (author)
Ozcelik, Hilmi (author)
Toland, Amanda E. (author)
Montagna, Marco (author)
D'Andrea, Emma (author)
Friedman, Eitan (author)
Laitman, Yael (author)
Borg, Åke (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Beattie, Mary (author)
Ramus, Susan J. (author)
Domchek, Susan M. (author)
Nathanson, Katherine L. (author)
Rebbeck, Tim (author)
Spurdle, Amanda B. (author)
Chen, Xiaoqing (author)
Holland, Helene (author)
John, Esther M. (author)
Hopper, John L. (author)
Buys, Saundra S. (author)
Daly, Mary B. (author)
Southey, Melissa C. (author)
Terry, Mary Beth (author)
Tung, Nadine (author)
Hansen, Thomas V. Overeem (author)
Nielsen, Finn C. (author)
Greene, Mark I. (author)
Mai, Phuong L. (author)
Osorio, Ana (author)
Duran, Mercedes (author)
Andres, Raquel (author)
Benitez, Javier (author)
Weitzel, Jeffrey N. (author)
Garber, Judy (author)
Hamann, Ute (author)
Peock, Susan (author)
Cook, Margaret (author)
Oliver, Clare (author)
Frost, Debra (author)
Platte, Radka (author)
Evans, D. Gareth (author)
Lalloo, Fiona (author)
Eeles, Ros (author)
Izatt, Louise (author)
Walker, Lisa (author)
Eason, Jacqueline (author)
Barwell, Julian (author)
Godwin, Andrew K. (author)
Schmutzler, Rita K. (author)
Wappenschmidt, Barbara (author)
Engert, Stefanie (author)
Arnold, Norbert (author)
Gadzicki, Dorothea (author)
Dean, Michael (author)
Gold, Bert (author)
Klein, Robert J. (author)
Couch, Fergus J. (author)
Chenevix-Trench, Georgia (author)
Easton, Douglas F. (author)
Daly, Mark J. (author)
Antoniou, Antonis C. (author)
Altshuler, David M. (author)
Offit, Kenneth (author)
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 (creator_code:org_t)
2010-10-28
2010
English.
In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (, 40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (lambda) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values, 10 25 and 39 SNPs had p-values<10(-4). These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, p = 3: 8 x 10(-5)) and for rs311499 was 0.72 (95% CI 0.61-0.85, p = 6: 6 x 10(-5)). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, p = 1: 2 x 10(-8)). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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By the author/editor
Gaudet, Mia M.
Kirchhoff, Tomas
Green, Todd
Vijai, Joseph
Korn, Joshua M.
Guiducci, Candac ...
show more...
Segre, Ayellet V ...
McGee, Kate
McGuffog, Lesley
Kartsonaki, Chri ...
Morrison, Jonath ...
Healey, Sue
Sinilnikova, Olg ...
Stoppa-Lyonnet, ...
Mazoyer, Sylvie
Gauthier-Villars ...
Sobol, Hagay
Longy, Michel
Frenay, Marc
Hogervorst, Fran ...
Rookus, Matti A.
Collee, J. Margr ...
Hoogerbrugge, Ni ...
van Roozendaal, ...
Piedmonte, Mario ...
Rubinstein, Wend ...
Nerenstone, Stac ...
Van Le, Linda
Blank, Stephanie ...
Caldes, Trinidad
de la Hoya, Migu ...
Nevanlinna, Heli
Aittomaki, Krist ...
Lazaro, Conxi
Blanco, Ignacio
Arason, Adalgeir
Johannsson, Oska ...
Barkardottir, Ro ...
Devilee, Peter
Olopade, Olofunm ...
Neuhausen, Susan ...
Wang, Xianshu
Fredericksen, Za ...
Peterlongo, Paol ...
Manoukian, Siran ...
Barile, Monica
Viel, Alessandra
Radice, Paolo
Phelan, Catherin ...
Narod, Steven
Rennert, Gad
Lejbkowicz, Flav ...
Flugelman, Anath
Andrulis, Irene ...
Glendon, Gord
Ozcelik, Hilmi
Toland, Amanda E ...
Montagna, Marco
D'Andrea, Emma
Friedman, Eitan
Laitman, Yael
Borg, Åke
Beattie, Mary
Ramus, Susan J.
Domchek, Susan M ...
Nathanson, Kathe ...
Rebbeck, Tim
Spurdle, Amanda ...
Chen, Xiaoqing
Holland, Helene
John, Esther M.
Hopper, John L.
Buys, Saundra S.
Daly, Mary B.
Southey, Melissa ...
Terry, Mary Beth
Tung, Nadine
Hansen, Thomas V ...
Nielsen, Finn C.
Greene, Mark I.
Mai, Phuong L.
Osorio, Ana
Duran, Mercedes
Andres, Raquel
Benitez, Javier
Weitzel, Jeffrey ...
Garber, Judy
Hamann, Ute
Peock, Susan
Cook, Margaret
Oliver, Clare
Frost, Debra
Platte, Radka
Evans, D. Gareth
Lalloo, Fiona
Eeles, Ros
Izatt, Louise
Walker, Lisa
Eason, Jacquelin ...
Barwell, Julian
Godwin, Andrew K ...
Schmutzler, Rita ...
Wappenschmidt, B ...
Engert, Stefanie
Arnold, Norbert
Gadzicki, Doroth ...
Dean, Michael
Gold, Bert
Klein, Robert J.
Couch, Fergus J.
Chenevix-Trench, ...
Easton, Douglas ...
Daly, Mark J.
Antoniou, Antoni ...
Altshuler, David ...
Offit, Kenneth
show less...
About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Cancer and Oncol ...
Articles in the publication
PLoS Genetics
By the university
Lund University

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