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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

Antoniou, Antonis C. (author)
Wang, Xianshu (author)
Fredericksen, Zachary S. (author)
show more...
McGuffog, Lesley (author)
Tarrell, Robert (author)
Sinilnikova, Olga M. (author)
Healey, Sue (author)
Morrison, Jonathan (author)
Kartsonaki, Christiana (author)
Lesnick, Timothy (author)
Ghoussaini, Maya (author)
Barrowdale, Daniel (author)
Peock, Susan (author)
Cook, Margaret (author)
Oliver, Clare (author)
Frost, Debra (author)
Eccles, Diana (author)
Evans, D. Gareth (author)
Eeles, Ros (author)
Izatt, Louise (author)
Chu, Carol (author)
Douglas, Fiona (author)
Paterson, Joan (author)
Stoppa-Lyonnet, Dominique (author)
Houdayer, Claude (author)
Mazoyer, Sylvie (author)
Giraud, Sophie (author)
Lasset, Christine (author)
Remenieras, Audrey (author)
Caron, Olivier (author)
Hardouin, Agnes (author)
Berthet, Pascaline (author)
Hogervorst, Frans B. L. (author)
Rookus, Matti A. (author)
Jager, Agnes (author)
van den Ouweland, Ans (author)
Hoogerbrugge, Nicoline (author)
van der Luijt, Rob B. (author)
Meijers-Heijboer, Hanne (author)
Garcia, Encarna B. Gomez (author)
Devilee, Peter (author)
Vreeswijk, Maaike P. G. (author)
Lubinski, Jan (author)
Jakubowska, Anna (author)
Gronwald, Jacek (author)
Huzarski, Tomasz (author)
Byrski, Tomasz (author)
Gorski, Bohdan (author)
Cybulski, Cezary (author)
Spurdle, Amanda B. (author)
Holland, Helene (author)
Goldgar, David E. (author)
John, Esther M. (author)
Hopper, John L. (author)
Southey, Melissa (author)
Buys, Saundra S. (author)
Daly, Mary B. (author)
Terry, Mary-Beth (author)
Schmutzler, Rita K. (author)
Wappenschmidt, Barbara (author)
Engel, Christoph (author)
Meindl, Alfons (author)
Preisler-Adams, Sabine (author)
Arnold, Norbert (author)
Niederacher, Dieter (author)
Sutter, Christian (author)
Domchek, Susan M. (author)
Nathanson, Katherine L. (author)
Rebbeck, Timothy (author)
Blum, Joanne L. (author)
Piedmonte, Marion (author)
Rodriguez, Gustavo C. (author)
Wakeley, Katie (author)
Boggess, John F. (author)
Basil, Jack (author)
Blank, Stephanie V. (author)
Friedman, Eitan (author)
Kaufman, Bella (author)
Laitman, Yael (author)
Milgrom, Roni (author)
Andrulis, Irene L. (author)
Glendon, Gord (author)
Ozcelik, Hilmi (author)
Kirchhoff, Tomas (author)
Vijai, Joseph (author)
Gaudet, Mia M. (author)
Altshuler, David (author)
Guiducci, Candace (author)
Loman, Niklas (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
Harbst, Katja (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
Rantala, Johanna (author)
Karolinska Institutet
Ehrencrona, Hans (author)
Uppsala universitet,Uppsala University,Institutionen för genetik och patologi
Gerdes, Anne-Marie (author)
Thomassen, Mads (author)
Sunde, Lone (author)
Peterlongo, Paolo (author)
Manoukian, Siranoush (author)
Bonanni, Bernardo (author)
Viel, Alessandra (author)
Radice, Paolo (author)
Caldes, Trinidad (author)
de la Hoya, Miguel (author)
Singer, Christian F. (author)
Fink-Retter, Anneliese (author)
Greene, Mark H. (author)
Mai, Phuong L. (author)
Loud, Jennifer T. (author)
Guidugli, Lucia (author)
Lindor, Noralane M. (author)
Hansen, Thomas V. O. (author)
Nielsen, Finn C. (author)
Blanco, Ignacio (author)
Lazaro, Conxi (author)
Garber, Judy (author)
Ramus, Susan J. (author)
Gayther, Simon A. (author)
Phelan, Catherine (author)
Narod, Stephen (author)
Szabo, Csilla I. (author)
Benitez, Javier (author)
Osorio, Ana (author)
Nevanlinna, Heli (author)
Heikkinen, Tuomas (author)
Caligo, Maria A. (author)
Beattie, Mary S. (author)
Hamann, Ute (author)
Godwin, Andrew K. (author)
Montagna, Marco (author)
Casella, Cinzia (author)
Neuhausen, Susan L. (author)
Karlan, Beth Y. (author)
Tung, Nadine (author)
Toland, Amanda E. (author)
Weitzel, Jeffrey (author)
Olopade, Olofunmilayo (author)
Simard, Jacques (author)
Soucy, Penny (author)
Rubinstein, Wendy S. (author)
Arason, Adalgeir (author)
Rennert, Gad (author)
Martin, Nicholas G. (author)
Montgomery, Grant W. (author)
Chang-Claude, Jenny (author)
Flesch-Janys, Dieter (author)
Brauch, Hiltrud (author)
Severi, Gianluca (author)
Baglietto, Laura (author)
Cox, Angela (author)
Cross, Simon S. (author)
Miron, Penelope (author)
Gerty, Sue M. (author)
Tapper, William (author)
Yannoukakos, Drakoulis (author)
Fountzilas, George (author)
Fasching, Peter A. (author)
Beckmann, Matthias W. (author)
Silva, Isabel dos Santos (author)
Peto, Julian (author)
Lambrechts, Diether (author)
Paridaens, Robert (author)
Ruediger, Thomas (author)
Foersti, Asta (author)
Winqvist, Robert (author)
Pylkaes, Katri (author)
Diasio, Robert B. (author)
Lee, Adam M. (author)
Eckel-Passow, Jeanette (author)
Vachon, Celine (author)
Blows, Fiona (author)
Driver, Kristy (author)
Dunning, Alison (author)
Pharoah, Paul P. D. (author)
Offit, Kenneth (author)
Pankratz, V. Shane (author)
Hakonarson, Hakon (author)
Chenevix-Trench, Georgia (author)
Easton, Douglas F. (author)
Couch, Fergus J. (author)
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 (creator_code:org_t)
2010-09-19
2010
English.
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.

Subject headings

Medical and Health Sciences  (hsv)
Clinical Medicine  (hsv)
Cancer and Oncology  (hsv)
Medicin och hälsovetenskap  (hsv)
Klinisk medicin  (hsv)
Cancer och onkologi  (hsv)
Basic Medicine  (hsv)
Medical Genetics  (hsv)
Medicinska grundvetenskaper  (hsv)
Medicinsk genetik  (hsv)

Keyword

Fine-scale mapping
Genetic risk factor
PTHLH
CCDC91
Breast cancer
BRAC1 mutation carriers

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By the author/editor
Antoniou, Antoni ...
Wang, Xianshu
Fredericksen, Za ...
McGuffog, Lesley
Tarrell, Robert
Sinilnikova, Olg ...
show more...
Healey, Sue
Morrison, Jonath ...
Kartsonaki, Chri ...
Lesnick, Timothy
Ghoussaini, Maya
Barrowdale, Dani ...
Peock, Susan
Cook, Margaret
Oliver, Clare
Frost, Debra
Eccles, Diana
Evans, D. Gareth
Eeles, Ros
Izatt, Louise
Chu, Carol
Douglas, Fiona
Paterson, Joan
Stoppa-Lyonnet, ...
Houdayer, Claude
Mazoyer, Sylvie
Giraud, Sophie
Lasset, Christin ...
Remenieras, Audr ...
Caron, Olivier
Hardouin, Agnes
Berthet, Pascali ...
Hogervorst, Fran ...
Rookus, Matti A.
Jager, Agnes
van den Ouweland ...
Hoogerbrugge, Ni ...
van der Luijt, R ...
Meijers-Heijboer ...
Garcia, Encarna ...
Devilee, Peter
Vreeswijk, Maaik ...
Lubinski, Jan
Jakubowska, Anna
Gronwald, Jacek
Huzarski, Tomasz
Byrski, Tomasz
Gorski, Bohdan
Cybulski, Cezary
Spurdle, Amanda ...
Holland, Helene
Goldgar, David E ...
John, Esther M.
Hopper, John L.
Southey, Melissa
Buys, Saundra S.
Daly, Mary B.
Terry, Mary-Beth
Schmutzler, Rita ...
Wappenschmidt, B ...
Engel, Christoph
Meindl, Alfons
Preisler-Adams, ...
Arnold, Norbert
Niederacher, Die ...
Sutter, Christia ...
Domchek, Susan M ...
Nathanson, Kathe ...
Rebbeck, Timothy
Blum, Joanne L.
Piedmonte, Mario ...
Rodriguez, Gusta ...
Wakeley, Katie
Boggess, John F.
Basil, Jack
Blank, Stephanie ...
Friedman, Eitan
Kaufman, Bella
Laitman, Yael
Milgrom, Roni
Andrulis, Irene ...
Glendon, Gord
Ozcelik, Hilmi
Kirchhoff, Tomas
Vijai, Joseph
Gaudet, Mia M.
Altshuler, David
Guiducci, Candac ...
Loman, Niklas
Harbst, Katja
Rantala, Johanna
Ehrencrona, Hans
Gerdes, Anne-Mar ...
Thomassen, Mads
Sunde, Lone
Peterlongo, Paol ...
Manoukian, Siran ...
Bonanni, Bernard ...
Viel, Alessandra
Radice, Paolo
Caldes, Trinidad
de la Hoya, Migu ...
Singer, Christia ...
Fink-Retter, Ann ...
Greene, Mark H.
Mai, Phuong L.
Loud, Jennifer T ...
Guidugli, Lucia
Lindor, Noralane ...
Hansen, Thomas V ...
Nielsen, Finn C.
Blanco, Ignacio
Lazaro, Conxi
Garber, Judy
Ramus, Susan J.
Gayther, Simon A ...
Phelan, Catherin ...
Narod, Stephen
Szabo, Csilla I.
Benitez, Javier
Osorio, Ana
Nevanlinna, Heli
Heikkinen, Tuoma ...
Caligo, Maria A.
Beattie, Mary S.
Hamann, Ute
Godwin, Andrew K ...
Montagna, Marco
Casella, Cinzia
Neuhausen, Susan ...
Karlan, Beth Y.
Tung, Nadine
Toland, Amanda E ...
Weitzel, Jeffrey
Olopade, Olofunm ...
Simard, Jacques
Soucy, Penny
Rubinstein, Wend ...
Arason, Adalgeir
Rennert, Gad
Martin, Nicholas ...
Montgomery, Gran ...
Chang-Claude, Je ...
Flesch-Janys, Di ...
Brauch, Hiltrud
Severi, Gianluca
Baglietto, Laura
Cox, Angela
Cross, Simon S.
Miron, Penelope
Gerty, Sue M.
Tapper, William
Yannoukakos, Dra ...
Fountzilas, Geor ...
Fasching, Peter ...
Beckmann, Matthi ...
Silva, Isabel do ...
Peto, Julian
Lambrechts, Diet ...
Paridaens, Rober ...
Ruediger, Thomas
Foersti, Asta
Winqvist, Robert
Pylkaes, Katri
Diasio, Robert B ...
Lee, Adam M.
Eckel-Passow, Je ...
Vachon, Celine
Blows, Fiona
Driver, Kristy
Dunning, Alison
Pharoah, Paul P. ...
Offit, Kenneth
Pankratz, V. Sha ...
Hakonarson, Hako ...
Chenevix-Trench, ...
Easton, Douglas ...
Couch, Fergus J.
show less...
About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Cancer and Oncol ...
Articles in the publication
Nature Genetics
By the university
Lund University
Karolinska Institutet
Uppsala University

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