Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers

被引：17

作者：

Maia, Ana-Teresa ^{[1
,2
,31
]}

Antoniou, Antonis C. ^{[3
]}

O'Reilly, Martin ^{[1
]}

Samarajiwa, Shamith ^{[1
,2
]}

Dunning, Mark ^{[1
]}

Kartsonaki, Christiana ^{[3
]}

Chin, Suet-Feung ^{[1
,2
]}

Curtis, Christina N. ^{[1
,2
,31
]}

McGuffog, Lesley ^{[3
]}

Domchek, Susan M. ^{[4
]}

Easton, Douglas F. ^{[3
]}

Peock, Susan ^{[3
]}

Frost, Debra ^{[3
]}

Evans, D. Gareth ^{[5
]}

Eeles, Ros ^{[6
,7
]}

Izatt, Louise ^{[8
]}

Adlard, Julian ^{[9
]}

Eccles, Diana ^{[10
]}

Sinilnikova, Olga M. ^{[12
,13
]}

Mazoyer, Sylvie ^{[12
]}

Stoppa-Lyonnet, Dominique ^{[14
,15
,16
]}

Gauthier-Villars, Marion ^{[14
]}

Faivre, Laurence ^{[17
,18
]}

Venat-Bouvet, Laurence ^{[19
]}

Delnatte, Capucine ^{[20
]}

Nevanlinna, Heli ^{[21
]}

Couch, Fergus J. ^{[22
]}

Godwin, Andrew K. ^{[23
]}

Caligo, Maria Adelaide ^{[24
,25
]}

Barkardottir, Rosa B. ^{[26
,27
]}

Chen, Xiaoqing ^{[29
]}

Beesley, Jonathan ^{[29
]}

Healey, Sue ^{[29
]}

Caldas, Carlos ^{[1
,2
,30
]}

Chenevix-Trench, Georgia ^{[29
]}

Ponder, Bruce A. J. ^{[1
,2
]}

机构：

[1] Li Ka Shing Ctr, Cambridge Res Inst CRUK, Cambridge CB2 0RE, England

[2] Univ Cambridge, Dept Oncol, Addenbrookes Hosp, Cambridge CB2 0RE, England

[3] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England

[4] Univ Penn, Dept Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[5] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester M13 9PL, Lancs, England

[6] Royal Marsden NHS Fdn Trust, Sutton SM2 5NG, Surrey, England

[7] Inst Canc Res, Oncogenet Team, Sutton SM2 5NG, Surrey, England

[8] Guys Hosp, Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England

[9] Chapel Allerton Hosp, Yorkshire Reg Genet Serv, Leeds LS7 4SA, W Yorkshire, England

[10] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton SO16 5YA, Hants, England

[11] Fed Natl Ctr Lutte Canc, GEMO Study Collaborators Canc Genet Network Grp G, Paris, France

[12] Univ Lyon 1, INSERM, U1052, CNRS,UMR5286,Res Ctr Lyon, F-69008 Lyon, France

[13] Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Ctr Hosp Univ Lyon, F-69008 Lyon, France

[14] Inst Curie, Serv Genet Oncol, F-75248 Paris 05, France

[15] Inst Curie, Unite INSERM U830, F-75248 Paris 05, France

[16] Univ Paris 05, Fac Med, F-75270 Paris 06, France

[17] Univ Bourgogne, Ctr Genet, CHU Dijon, F-21000 Dijon, France

[18] Ctr Georges Francois Leclerc, F-21000 Dijon, France

[19] Ctr Hosp Univ Dupuytren, Dept Med Oncol, Limoges, France

[20] Ctr Rene Gauducheau, F-44805 Nantes, France

[21] Univ Helsinki, Dept Obstet & Gynecol, Cent Hosp, Helsinki 00029, Finland

[22] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA

[23] Univ Kansas, Med Ctr, Ks City, KS 66160 USA

[24] Univ Pisa, Div Surg Mol & Ultrastruct Pathol, Dept Oncol, I-56126 Pisa, Italy

[25] Pisa Univ Hosp, I-56126 Pisa, Italy

[26] Landspitali Univ Hosp, Dept Pathol, IS-101 Reykjavik, Iceland

[27] Univ Iceland, Fac Med, Reykjavik, Iceland

[28] Peter MacCallum Canc Inst, Melbourne, Vic 8006, Australia

[29] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[30] Li Ka Shing Ctr, Cambridge Expt Canc Med Ctr, Cambridge CB2 0RE, England

[31] Univ Algarve, Inst Biotechnol & Bioengn, Ctr Mol & Struct Biomed, Dept Biomed Sci & Med, P-8005139 Faro, Portugal

来源：

BREAST CANCER RESEARCH | 2012年 / 14卷 / 02期

基金：

芬兰科学院; 澳大利亚国家健康与医学研究理事会;

关键词：

GENE-EXPRESSION; CELL-LINE; COLORECTAL-CANCER; ALLELIC IMBALANCE; HUMAN GENOME; COMMON; PREDISPOSITION; ASSOCIATION; BEADARRAY; CARCINOMA;

D O I：

10.1186/bcr3169

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Cis-acting regulatory single nucleotide polymorphisms (SNPs) at specific loci may modulate penetrance of germline mutations at the same loci by introducing different levels of expression of the wild-type allele. We have previously reported that BRCA2 shows differential allelic expression and we hypothesize that the known variable penetrance of BRCA2 mutations might be associated with this mechanism. Methods: We combined haplotype analysis and differential allelic expression of BRCA2 in breast tissue to identify expression haplotypes and candidate cis-regulatory variants. These candidate variants underwent selection based on in silico predictions for regulatory potential and disruption of transcription factor binding, and were functionally analyzed in vitro and in vivo in normal and breast cancer cell lines. SNPs tagging the expression haplotypes were correlated with the total expression of several genes in breast tissue measured by Taqman and microarray technologies. The effect of the expression haplotypes on breast cancer risk in BRCA2 mutation carriers was investigated in 2,754 carriers. Results: We identified common haplotypes associated with differences in the levels of BRCA2 expression in human breast cells. We characterized three cis-regulatory SNPs located at the promoter and two intronic regulatory elements which affect the binding of the transcription factors C/EBP alpha, HMGA1, D-binding protein (DBP) and ZF5. We showed that the expression haplotypes also correlated with changes in the expression of other genes in normal breast. Furthermore, there was suggestive evidence that the minor allele of SNP rs4942440, which is associated with higher BRCA2 expression, is also associated with a reduced risk of breast cancer (per-allele hazard ratio (HR) = 0.85, 95% confidence interval (CI) = 0.72 to 1.00, P-trend = 0.048). Conclusions: Our work provides further insights into the role of cis-regulatory variation in the penetrance of disease-causing mutations. We identified small-effect genetic variants associated with allelic expression differences in BRCA2 which could possibly affect the risk in mutation carriers through altering expression levels of the wild-type allele.

引用

页数：15

共 47 条

[1] Subtle variations in Pten dose determine cancer susceptibility [J].

Alimonti, Andrea ;

Carracedo, Arkaitz ;

Clohessy, John G. ;

Trotman, Lloyd C. ;

Nardella, Caterina ;

Egia, Ainara ;

Salmena, Leonardo ;

Sampieri, Katia ;

Haveman, William J. ;

Brogi, Edi ;

Richardson, Andrea L. ;

Zhang, Jiangwen ;

Pandolfi, Pier Paolo .

NATURE GENETICS, 2010, 42 (05) :454-U136

[2] A haplotype map of the human genome [J].

Altshuler, D ;

Brooks, LD ;

Chakravarti, A ;

Collins, FS ;

Daly, MJ ;

Donnelly, P ;

Gibbs, RA ;

Belmont, JW ;

Boudreau, A ;

Leal, SM ;

Hardenbol, P ;

Pasternak, S ;

Wheeler, DA ;

Willis, TD ;

Yu, FL ;

Yang, HM ;

Zeng, CQ ;

Gao, Y ;

Hu, HR ;

Hu, WT ;

Li, CH ;

Lin, W ;

Liu, SQ ;

Pan, H ;

Tang, XL ;

Wang, J ;

Wang, W ;

Yu, J ;

Zhang, B ;

Zhang, QR ;

Zhao, HB ;

Zhao, H ;

Zhou, J ;

Gabriel, SB ;

Barry, R ;

Blumenstiel, B ;

Camargo, A ;

Defelice, M ;

Faggart, M ;

Goyette, M ;

Gupta, S ;

Moore, J ;

Nguyen, H ;

Onofrio, RC ;

Parkin, M ;

Roy, J ;

Stahl, E ;

Winchester, E ;

Ziaugra, L ;

Shen, Y .

NATURE, 2005, 437 (7063) :1299-1320

[3] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[4]

[Anonymous], 2010, R LANG ENV STAT COMP

[5] Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history:: A combined analysis of 22 studies [J].

Antoniou, A ;

Pharoah, PDP ;

Narod, S ;

Risch, HA ;

Eyfjord, JE ;

Hopper, JL ;

Loman, N ;

Olsson, H ;

Johannsson, O ;

Borg, Å ;

Pasini, B ;

Radice, P ;

Manoukian, S ;

Eccles, DM ;

Tang, N ;

Olah, E ;

Anton-Culver, H ;

Warner, E ;

Lubinski, J ;

Gronwald, J ;

Gorski, B ;

Tulinius, H ;

Thorlacius, S ;

Eerola, H ;

Nevanlinna, H ;

Syrjäkoski, K ;

Kallioniemi, OP ;

Thompson, D ;

Evans, C ;

Peto, J ;

Lalloo, F ;

Evans, DG ;

Easton, DF .

AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 72 (05) :1117-1130

[6] Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers [J].

Antoniou, Antonis C. ;

Spurdle, Amanda B. ;

Sinilnikova, Olga M. ;

Healey, Sue ;

Pooley, Karen A. ;

Schmutzler, Rita K. ;

Versmold, Beatrix ;

Engel, Christoph ;

Meindl, Alfons ;

Arnold, Norbert ;

Hofmann, Wera ;

Sutter, Christian ;

Niederacher, Dieter ;

Deissler, Helmut ;

Caldes, Trinidad ;

Kampjarvi, Kati ;

Nevanlinna, Heli ;

Simard, Jacques ;

Beesley, Jonathan ;

Chen, Xiaoqing ;

Neuhausen, Susan L. ;

Rebbeck, Timothy R. ;

Wagner, Theresa ;

Lynch, Henry T. ;

Isaacs, Claudine ;

Weitzel, Jeffrey ;

Ganz, Patricia A. ;

Daly, Mary B. ;

Tomlinson, Gail ;

Olopade, Olufunmilayo I. ;

Bium, Joanne L. ;

Couch, Fergus J. ;

Peterlongo, Paolo ;

Manoukian, Siranoush ;

Barile, Monica ;

Radice, Paolo ;

Szabo, Csilla I. ;

Pereira, Lutecia H. Mateus ;

Greene, Mark H. ;

Rennert, Gad ;

Leibkowicz, Flavio ;

Barnett-Griness, Ofra ;

Andrulis, Irene L. ;

Ozcelik, Hilmi ;

Gerdes, Anne-Marie ;

Caligo, Maria A. ;

Laitman, Yael ;

Kaufman, Bella ;

Milgrom, Roni ;

Friedman, Eitan .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (04) :937-948

[7] RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers:: Results from a combined analysis of 19 studies [J].

Antoniou, Antonis C. ;

Sinilnikova, Olga M. ;

Simard, Jacques ;

Leone, Melanie ;

Dumont, Martine ;

Neuhausen, Susan L. ;

Struewing, Jeffery P. ;

Stoppa-Lyonnet, Dominique ;

Barjhoux, Laure ;

Hughes, David J. ;

Coupier, Isabelle ;

Belotti, Muriel ;

Lasset, Christine ;

Rebbeck, Timothy R. ;

Wagner, Theresa ;

Lynch, Henry T. ;

Domchek, Susan M. ;

Nathanson, Katherine L. ;

Garber, Judy E. ;

Weitzel, Jeffrey ;

Narod, Steven A. ;

Tomlinson, Gail ;

Olopade, Olufunmilayo I. ;

Godwin, Andrew ;

Isaacs, Claudine ;

Jakubowska, Anna ;

Lubinski, Jan ;

Gronwald, Jacek ;

Gorski, Bohdan ;

Byrski, Tomasz ;

Huzarski, Tomasz ;

Peock, Susan ;

Cook, Margaret ;

Baynes, Caroline ;

Murray, Alexandra ;

Rogers, Mark ;

Daly, Peter A. ;

Dorkins, Huw ;

Schmutzler, Rita K. ;

Versmold, Beatrix ;

Engel, Christoph ;

Meindl, Alfons ;

Arnold, Norbert ;

Niederacher, Dieter ;

Deissler, Helmut ;

Spurdle, Amanda B. ;

Chen, Xiaoqing ;

Waddell, Nicola ;

Cloonan, Nicole ;

Kirchhoff, Tomas .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (06) :1186-1200

[8] Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction [J].

Antoniou, Antonis C. ;

Beesley, Jonathan ;

McGuffog, Lesley ;

Sinilnikova, Olga M. ;

Healey, Sue ;

Neuhausen, Susan L. ;

Ding, Yuan Chun ;

Rebbeck, Timothy R. ;

Weitzel, Jeffrey N. ;

Lynch, Henry T. ;

Isaacs, Claudine ;

Ganz, Patricia A. ;

Tomlinson, Gail ;

Olopade, Olufunmilayo I. ;

Couch, Fergus J. ;

Wang, Xianshu ;

Lindor, Noralane M. ;

Pankratz, Vernon S. ;

Radice, Paolo ;

Manoukian, Siranoush ;

Peissel, Bernard ;

Zaffaroni, Daniela ;

Barile, Monica ;

Viel, Alessandra ;

Allavena, Anna ;

Dall'Olio, Valentina ;

Peterlongo, Paolo ;

Szabo, Csilla I. ;

Zikan, Michal ;

Claes, Kathleen ;

Poppe, Bruce ;

Foretova, Lenka ;

Mai, Phuong L. ;

Greene, Mark H. ;

Rennert, Gad ;

Lejbkowicz, Flavio ;

Glendon, Gord ;

Ozcelik, Hilmi ;

Andrulis, Irene L. ;

Thomassen, Mads ;

Gerdes, Anne-Marie ;

Sunde, Lone ;

Cruger, Dorthe ;

Jensen, Uffe Birk ;

Caligo, Maria ;

Friedman, Eitan ;

Kaufman, Bella ;

Laitman, Yael ;

Milgrom, Roni ;

Dubrovsky, Maya .

CANCER RESEARCH, 2010, 70 (23) :9742-9754

[9] Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers [J].

Antoniou, Antonis C. ;

Sinilnikova, Olga M. ;

McGuffog, Lesley ;

Healey, Sue ;

Nevanlinna, Heli ;

Heikkinen, Tuomas ;

Simard, Jacques ;

Spurdle, Amanda B. ;

Beesley, Jonathan ;

Chen, Xiaoqing ;

Neuhausen, Susan L. ;

Ding, Yuan C. ;

Couch, Fergus J. ;

Wang, Xianshu ;

Fredericksen, Zachary ;

Peterlongo, Paolo ;

Peissel, Bernard ;

Bonanni, Bernardo ;

Viel, Alessandra ;

Bernard, Loris ;

Radice, Paolo ;

Szabo, Csilla I. ;

Foretova, Lenka ;

Zikan, Michal ;

Claes, Kathleen ;

Greene, Mark H. ;

Mai, Phuong L. ;

Rennert, Gad ;

Lejbkowicz, Flavio ;

Andrulis, Irene L. ;

Ozcelik, Hilmi ;

Glendon, Gord ;

Gerdes, Anne-Marie ;

Thomassen, Mads ;

Sunde, Lone ;

Caligo, Maria A. ;

Laitman, Yael ;

Kontorovich, Tair ;

Cohen, Shimrit ;

Kaufman, Bella ;

Dagan, Efrat ;

Baruch, Ruth Gershoni ;

Friedman, Eitan ;

Harbst, Katja ;

Barbany-Bustinza, Gisela ;

Rantala, Johanna ;

Ehrencrona, Hans ;

Karlsson, Per ;

Domchek, Susan M. ;

Nathanson, Katherine L. .

HUMAN MOLECULAR GENETICS, 2009, 18 (22) :4442-4456

[10] Lower level of BRCA2 protein in heterozygous mutation carriers is correlated with an increase in DNA double strand breaks and an impaired DSB repair [J].

Arnold, Katrin ;

Kim, Min-Kyoung ;

Frerk, Katrin ;

Edler, Lutz ;

Savelyeva, Larissa ;

Schmezer, Peter ;

Wiedemeyer, Ruprecht .

CANCER LETTERS, 2006, 243 (01) :90-100

← 1 2 3 4 5 →

共 47 条

[1] Subtle variations in Pten dose determine cancer susceptibility [J].

Alimonti, Andrea ;

Carracedo, Arkaitz ;

Clohessy, John G. ;

Trotman, Lloyd C. ;

Nardella, Caterina ;

Egia, Ainara ;

Salmena, Leonardo ;

Sampieri, Katia ;

Haveman, William J. ;

Brogi, Edi ;

Richardson, Andrea L. ;

Zhang, Jiangwen ;

Pandolfi, Pier Paolo .

NATURE GENETICS, 2010, 42 (05) :454-U136

[2] A haplotype map of the human genome [J].

Altshuler, D ;

Brooks, LD ;

Chakravarti, A ;

Collins, FS ;

Daly, MJ ;

Donnelly, P ;

Gibbs, RA ;

Belmont, JW ;

Boudreau, A ;

Leal, SM ;

Hardenbol, P ;

Pasternak, S ;

Wheeler, DA ;

Willis, TD ;

Yu, FL ;

Yang, HM ;

Zeng, CQ ;

Gao, Y ;

Hu, HR ;

Hu, WT ;

Li, CH ;

Lin, W ;

Liu, SQ ;

Pan, H ;

Tang, XL ;

Wang, J ;

Wang, W ;

Yu, J ;

Zhang, B ;

Zhang, QR ;

Zhao, HB ;

Zhao, H ;

Zhou, J ;

Gabriel, SB ;

Barry, R ;

Blumenstiel, B ;

Camargo, A ;

Defelice, M ;

Faggart, M ;

Goyette, M ;

Gupta, S ;

Moore, J ;

Nguyen, H ;

Onofrio, RC ;

Parkin, M ;

Roy, J ;

Stahl, E ;

Winchester, E ;

Ziaugra, L ;

Shen, Y .

NATURE, 2005, 437 (7063) :1299-1320

[3] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[4]

[Anonymous], 2010, R LANG ENV STAT COMP

[5] Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history:: A combined analysis of 22 studies [J].

Antoniou, A ;

Pharoah, PDP ;

Narod, S ;

Risch, HA ;

Eyfjord, JE ;

Hopper, JL ;

Loman, N ;

Olsson, H ;

Johannsson, O ;

Borg, Å ;

Pasini, B ;

Radice, P ;

Manoukian, S ;

Eccles, DM ;

Tang, N ;

Olah, E ;

Anton-Culver, H ;

Warner, E ;

Lubinski, J ;

Gronwald, J ;

Gorski, B ;

Tulinius, H ;

Thorlacius, S ;

Eerola, H ;

Nevanlinna, H ;

Syrjäkoski, K ;

Kallioniemi, OP ;

Thompson, D ;

Evans, C ;

Peto, J ;

Lalloo, F ;

Evans, DG ;

Easton, DF .

AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 72 (05) :1117-1130

[6] Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers [J].

Antoniou, Antonis C. ;

Spurdle, Amanda B. ;

Sinilnikova, Olga M. ;

Healey, Sue ;

Pooley, Karen A. ;

Schmutzler, Rita K. ;

Versmold, Beatrix ;

Engel, Christoph ;

Meindl, Alfons ;

Arnold, Norbert ;

Hofmann, Wera ;

Sutter, Christian ;

Niederacher, Dieter ;

Deissler, Helmut ;

Caldes, Trinidad ;

Kampjarvi, Kati ;

Nevanlinna, Heli ;

Simard, Jacques ;

Beesley, Jonathan ;

Chen, Xiaoqing ;

Neuhausen, Susan L. ;

Rebbeck, Timothy R. ;

Wagner, Theresa ;

Lynch, Henry T. ;

Isaacs, Claudine ;

Weitzel, Jeffrey ;

Ganz, Patricia A. ;

Daly, Mary B. ;

Tomlinson, Gail ;

Olopade, Olufunmilayo I. ;

Bium, Joanne L. ;

Couch, Fergus J. ;

Peterlongo, Paolo ;

Manoukian, Siranoush ;

Barile, Monica ;

Radice, Paolo ;

Szabo, Csilla I. ;

Pereira, Lutecia H. Mateus ;

Greene, Mark H. ;

Rennert, Gad ;

Leibkowicz, Flavio ;

Barnett-Griness, Ofra ;

Andrulis, Irene L. ;

Ozcelik, Hilmi ;

Gerdes, Anne-Marie ;

Caligo, Maria A. ;

Laitman, Yael ;

Kaufman, Bella ;

Milgrom, Roni ;

Friedman, Eitan .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (04) :937-948

[7] RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers:: Results from a combined analysis of 19 studies [J].

Antoniou, Antonis C. ;

Sinilnikova, Olga M. ;

Simard, Jacques ;

Leone, Melanie ;

Dumont, Martine ;

Neuhausen, Susan L. ;

Struewing, Jeffery P. ;

Stoppa-Lyonnet, Dominique ;

Barjhoux, Laure ;

Hughes, David J. ;

Coupier, Isabelle ;

Belotti, Muriel ;

Lasset, Christine ;

Rebbeck, Timothy R. ;

Wagner, Theresa ;

Lynch, Henry T. ;

Domchek, Susan M. ;

Nathanson, Katherine L. ;

Garber, Judy E. ;

Weitzel, Jeffrey ;

Narod, Steven A. ;

Tomlinson, Gail ;

Olopade, Olufunmilayo I. ;

Godwin, Andrew ;

Isaacs, Claudine ;

Jakubowska, Anna ;

Lubinski, Jan ;

Gronwald, Jacek ;

Gorski, Bohdan ;

Byrski, Tomasz ;

Huzarski, Tomasz ;

Peock, Susan ;

Cook, Margaret ;

Baynes, Caroline ;

Murray, Alexandra ;

Rogers, Mark ;

Daly, Peter A. ;

Dorkins, Huw ;

Schmutzler, Rita K. ;

Versmold, Beatrix ;

Engel, Christoph ;

Meindl, Alfons ;

Arnold, Norbert ;

Niederacher, Dieter ;

Deissler, Helmut ;

Spurdle, Amanda B. ;

Chen, Xiaoqing ;

Waddell, Nicola ;

Cloonan, Nicole ;

Kirchhoff, Tomas .

AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 81 (06) :1186-1200

[8] Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction [J].

Antoniou, Antonis C. ;

Beesley, Jonathan ;

McGuffog, Lesley ;

Sinilnikova, Olga M. ;

Healey, Sue ;

Neuhausen, Susan L. ;

Ding, Yuan Chun ;

Rebbeck, Timothy R. ;

Weitzel, Jeffrey N. ;

Lynch, Henry T. ;

Isaacs, Claudine ;

Ganz, Patricia A. ;

Tomlinson, Gail ;

Olopade, Olufunmilayo I. ;

Couch, Fergus J. ;

Wang, Xianshu ;

Lindor, Noralane M. ;

Pankratz, Vernon S. ;

Radice, Paolo ;

Manoukian, Siranoush ;

Peissel, Bernard ;

Zaffaroni, Daniela ;

Barile, Monica ;

Viel, Alessandra ;

Allavena, Anna ;

Dall'Olio, Valentina ;

Peterlongo, Paolo ;

Szabo, Csilla I. ;

Zikan, Michal ;

Claes, Kathleen ;

Poppe, Bruce ;

Foretova, Lenka ;

Mai, Phuong L. ;

Greene, Mark H. ;

Rennert, Gad ;

Lejbkowicz, Flavio ;

Glendon, Gord ;

Ozcelik, Hilmi ;

Andrulis, Irene L. ;

Thomassen, Mads ;

Gerdes, Anne-Marie ;

Sunde, Lone ;

Cruger, Dorthe ;

Jensen, Uffe Birk ;

Caligo, Maria ;

Friedman, Eitan ;

Kaufman, Bella ;

Laitman, Yael ;

Milgrom, Roni ;

Dubrovsky, Maya .

CANCER RESEARCH, 2010, 70 (23) :9742-9754

[9] Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers [J].

Antoniou, Antonis C. ;

Sinilnikova, Olga M. ;

McGuffog, Lesley ;

Healey, Sue ;

Nevanlinna, Heli ;

Heikkinen, Tuomas ;

Simard, Jacques ;

Spurdle, Amanda B. ;

Beesley, Jonathan ;

Chen, Xiaoqing ;

Neuhausen, Susan L. ;

Ding, Yuan C. ;

Couch, Fergus J. ;

Wang, Xianshu ;

Fredericksen, Zachary ;

Peterlongo, Paolo ;

Peissel, Bernard ;

Bonanni, Bernardo ;

Viel, Alessandra ;

Bernard, Loris ;

Radice, Paolo ;

Szabo, Csilla I. ;

Foretova, Lenka ;

Zikan, Michal ;

Claes, Kathleen ;

Greene, Mark H. ;

Mai, Phuong L. ;

Rennert, Gad ;

Lejbkowicz, Flavio ;

Andrulis, Irene L. ;

Ozcelik, Hilmi ;

Glendon, Gord ;

Gerdes, Anne-Marie ;

Thomassen, Mads ;

Sunde, Lone ;

Caligo, Maria A. ;

Laitman, Yael ;

Kontorovich, Tair ;

Cohen, Shimrit ;

Kaufman, Bella ;

Dagan, Efrat ;

Baruch, Ruth Gershoni ;

Friedman, Eitan ;

Harbst, Katja ;

Barbany-Bustinza, Gisela ;

Rantala, Johanna ;

Ehrencrona, Hans ;

Karlsson, Per ;

Domchek, Susan M. ;

Nathanson, Katherine L. .

HUMAN MOLECULAR GENETICS, 2009, 18 (22) :4442-4456

[10] Lower level of BRCA2 protein in heterozygous mutation carriers is correlated with an increase in DNA double strand breaks and an impaired DSB repair [J].

Arnold, Katrin ;

Kim, Min-Kyoung ;

Frerk, Katrin ;

Edler, Lutz ;

Savelyeva, Larissa ;

Schmezer, Peter ;

Wiedemeyer, Ruprecht .

CANCER LETTERS, 2006, 243 (01) :90-100

← 1 2 3 4 5 →