RAD51B in Familial Breast Cancer

被引：21

作者：

Pelttari, Liisa M. ^{[1
,2
]}

Khan, Sofia ^{[1
,2
]}

Vuorela, Mikko ^{[3
]}

Kiiski, Johanna I. ^{[1
,2
]}

Vilske, Sara ^{[1
,2
]}

Nevanlinna, Viivi ^{[1
,2
]}

Ranta, Salla ^{[1
,2
]}

Schleutker, Johanna ^{[4
,5
,6
]}

Winqvist, Robert ^{[3
,7
]}

Kallioniemi, Anne ^{[4
,8
]}

Doerk, Thilo ^{[9
]}

Bogdanova, Natalia V. ^{[10
]}

Figueroa, Jonine ^{[11
]}

Pharoah, Paul D. P. ^{[12
,13
]}

Schmidt, Marjanka K. ^{[14
]}

Dunning, Alison M. ^{[12
]}

Garcia-Closas, Montserrat ^{[11
,15
]}

Bolla, Manjeet K. ^{[13
]}

Dennis, Joe ^{[13
]}

Michailidou, Kyriaki ^{[13
]}

Wang, Qin ^{[13
]}

Hopper, John L. ^{[16
]}

Southey, Melissa C. ^{[17
]}

Rosenberg, Efraim H. ^{[14
]}

Fasching, Peter A. ^{[18
,19
]}

Beckmann, Matthias W. ^{[18
]}

Peto, Julian ^{[20
]}

dos-Santos-Silva, Isabel ^{[20
]}

Sawyer, Elinor J. ^{[21
]}

Tomlinson, Ian ^{[22
,23
]}

Burwinkel, Barbara ^{[24
,25
]}

Surowy, Harald ^{[24
,25
]}

Guenel, Pascal ^{[26
,27
]}

Truong, Therese ^{[26
,27
]}

Bojesen, Stig E. ^{[28
,29
,30
]}

Nordestgaard, Borge G. ^{[29
,30
]}

Benitez, Javier ^{[31
,32
]}

Gonzalez-Neira, Anna ^{[31
]}

Neuhausen, Susan L. ^{[33
]}

Anton-Culver, Hoda ^{[34
]}

Brenner, Hermann ^{[35
,36
,37
,38
]}

Arndt, Volker ^{[35
]}

Meindl, Alfons ^{[39
]}

Schmutzler, Rita K. ^{[40
,41
,42
]}

Brauch, Hiltrud ^{[36
,43
,44
]}

Bruening, Thomas ^{[45
]}

Lindblom, Annika ^{[46
]}

Margolin, Sara ^{[47
]}

Mannermaa, Arto ^{[48
,49
,50
]}

Hartikainen, Jaana M. ^{[48
,49
,50
]}

机构：

[1] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland

[2] Helsinki Univ Hosp, Helsinki, Finland

[3] Univ Oulu, Bioctr Oulu, Lab Canc Genet & Tumor Biol, Canc Res & Translat Med, Oulu, Finland

[4] Univ Tampere, BioMediTech, FIN-33101 Tampere, Finland

[5] Univ Turku, Dept Med Biochem & Genet, Turku, Finland

[6] Turku Univ Hosp, Dept Med Genet, Tyks Microbiol & Genet, FIN-20520 Turku, Finland

[7] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu, Finland

[8] Fimlab Labs, Tampere, Finland

[9] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany

[10] Hannover Med Sch, Radiat Oncol Res Unit, Hannover, Germany

[11] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA

[12] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England

[13] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England

[14] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands

[15] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England

[16] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia

[17] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia

[18] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Obstet & Gynaecol, D-91054 Erlangen, Germany

[19] Univ Calif Los Angeles, Dept Med, Div Hematol & Oncol, David Geffen Sch Med, Los Angeles, CA 90024 USA

[20] London Sch Hyg & Trop Med, Dept Noncommun Dis Epidemiol, London WC1, England

[21] Kings Coll London, Guys Hosp, Res Oncol, London WC2R 2LS, England

[22] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[23] Univ Oxford, Oxford NIHR Biomed Res Ctr, Oxford, England

[24] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany

[25] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany

[26] INSERM, Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc, Villejuif, France

[27] Univ Paris 11, Villejuif, France

[28] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Herlev, Denmark

[29] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark

[30] Univ Copenhagen, Fac Med & Hlth Sci, Copenhagen, Denmark

[31] Spanish Natl Canc Res Ctr, Human Canc Genet Program, Madrid, Spain

[32] Ctr Invest Red Enfermedades Raras, Valencia, Spain

[33] Beckman Res Inst City Hope, Duarte, CA USA

[34] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA

[35] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[36] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[37] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany

[38] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[39] Tech Univ Munich, Div Gynaecol & Obstet, D-80290 Munich, Germany

[40] Univ Hosp Cologne, Ctr Hereditary Breast & Ovarian Canc, Cologne, Germany

[41] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany

[42] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany

[43] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany

[44] Univ Tubingen, Tubingen, Germany

[45] Ruhr Univ Bochum, German Social Accid Insurance Inst, Inst Prevent & Occupat Med, Univ Str 150, Bochum, Germany

[46] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[47] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden

[48] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland

[49] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland

[50] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland

来源：

PLOS ONE | 2016年 / 11卷 / 05期

基金：

芬兰科学院; 美国国家卫生研究院; 英国医学研究理事会; 加拿大健康研究院;

关键词：

GENOME-WIDE ASSOCIATION; CONFER SUSCEPTIBILITY; GERMLINE MUTATIONS; OVARIAN; RISK; XRCC2; GENE; VARIANTS; ALLELES; COMPLEX;

D O I：

10.1371/journal.pone.0153788

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10(-16)) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10(-11)), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.

引用

页数：18

共 33 条

[1] Identification of a novel human RAD51 homolog, RAD51B [J].

Albala, JS ;

Thelen, MP ;

Prange, C ;

Fan, WF ;

Christensen, M ;

Thompson, LH ;

Lennon, GG .

GENOMICS, 1997, 46 (03) :476-479

[2] Rad51 Paralog Complexes BCDX2 and CX3 Act at Different Stages in the BRCA1-BRCA2-Dependent Homologous Recombination Pathway [J].

Chun, Jarin ;

Buechelmaier, Erika S. ;

Powell, Simon N. .

MOLECULAR AND CELLULAR BIOLOGY, 2013, 33 (02) :387-395

[3] Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk [J].

Couch, Fergus J. ;

Wang, Xianshu ;

McGuffog, Lesley ;

Lee, Andrew ;

Olswold, Curtis ;

Kuchenbaecker, Karoline B. ;

Soucy, Penny ;

Fredericksen, Zachary ;

Barrowdale, Daniel ;

Dennis, Joe ;

Gaudet, Mia M. ;

Dicks, Ed ;

Kosel, Matthew ;

Healey, Sue ;

Sinilnikova, Olga M. ;

Lee, Adam ;

Bacot, Francois ;

Vincent, Daniel ;

Hogervorst, Frans B. L. ;

Peock, Susan ;

Stoppa-Lyonnet, Dominique ;

Jakubowska, Anna ;

Radice, Paolo ;

Schmutzler, Rita Katharina ;

Domchek, Susan M. ;

Piedmonte, Marion ;

Singer, Christian F. ;

Friedman, Eitan ;

Thomassen, Mads ;

Hansen, Thomas V. O. ;

Neuhausen, Susan L. ;

Szabo, Csilla I. ;

Blanco, Ignacio ;

Greene, Mark H. ;

Karlan, Beth Y. ;

Garber, Judy ;

Phelan, Catherine M. ;

Weitzel, Jeffrey N. ;

Montagna, Marco ;

Olah, Edith ;

Andrulis, Irene L. ;

Godwin, Andrew K. ;

Yannoukakos, Drakoulis ;

Goldgar, David E. ;

Caldes, Trinidad ;

Nevanlinna, Heli ;

Osorio, Ana ;

Terry, Mary Beth ;

Daly, Mary B. ;

van Rensburg, Elizabeth J. .

PLOS GENETICS, 2013, 9 (03)

[4] Haploinsufficiency of RAD51B causes centrosome fragmentation and aneuploidy in human cells [J].

Date, Osamu ;

Katsura, Mari ;

Ishida, Mari ;

Yoshihara, Takashi ;

Kinomura, Aiko ;

Sueda, Taijiro ;

Miyagawa, Kiyoshi .

CANCER RESEARCH, 2006, 66 (12) :6018-6024

[5] Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium [J].

Figueroa, Jonine D. ;

Garcia-Closas, Montserrat ;

Humphreys, Manjeet ;

Platte, Radka ;

Hopper, John L. ;

Southey, Melissa C. ;

Apicella, Carmel ;

Hammet, Fleur ;

Schmidt, Marjanka K. ;

Broeks, Annegien ;

Tollenaar, Rob A. E. M. ;

Van't Veer, Laura J. ;

Fasching, Peter A. ;

Beckmann, Matthias W. ;

Ekici, Arif B. ;

Strick, Reiner ;

Peto, Julian ;

Silva, Isabel dos Santos ;

Fletcher, Olivia ;

Johnson, Nichola ;

Sawyer, Elinor ;

Tomlinson, Ian ;

Kerin, Michael ;

Burwinkel, Barbara ;

Marme, Federik ;

Schneeweiss, Andreas ;

Sohn, Christof ;

Bojesen, Stig ;

Flyger, Henrik ;

Nordestgaard, Borge G. ;

Benitez, Javier ;

Milne, Roger L. ;

Ignacio Arias, Jose ;

Pilar Zamora, M. ;

Brenner, Hermann ;

Mueller, Heiko ;

Arndt, Volker ;

Rahman, Nazneen ;

Turnbull, Clare ;

Seal, Sheila ;

Renwick, Anthony ;

Brauch, Hiltrud ;

Justenhoven, Christina ;

Bruening, Thomas ;

Chang-Claude, Jenny ;

Hein, Rebecca ;

Wang-Gohrke, Shan ;

Doerk, Thilo ;

Schuermann, Peter ;

Bremer, Michael .

HUMAN MOLECULAR GENETICS, 2011, 20 (23) :4693-4706

[6] Germline mutation in the RAD51B gene confers predisposition to breast cancer [J].

Golmard, Lisa ;

Caux-Moncoutier, Virginie ;

Davy, Gregoire ;

Al Ageeli, Essam ;

Poirot, Brigitte ;

Tirapo, Carole ;

Michaux, Dorothee ;

Barbaroux, Catherine ;

d'Enghien, Catherine Dubois ;

Nicolas, Andre ;

Castera, Laurent ;

Sastre-Garau, Xavier ;

Stern, Marc-Henri ;

Houdayer, Claude ;

Stoppa-Lyonnet, Dominique .

BMC CANCER, 2013, 13

[7] Rare variants in XRCC2 as breast cancer susceptibility alleles [J].

Hilbers, Florentine S. ;

Wijnen, Juul T. ;

Hoogerbrugge, Nicoline ;

Oosterwijk, Jan C. ;

Collee, Margriet J. ;

Peterlongo, Paolo ;

Radice, Paolo ;

Manoukian, Siranoush ;

Feroce, Irene ;

Capra, Fabio ;

Couch, Fergus J. ;

Wang, Xianshu ;

Guidugli, Lucia ;

Offit, Kenneth ;

Shah, Sohela ;

Campbell, Ian G. ;

Thompson, Ella R. ;

James, Paul A. ;

Trainer, Alison H. ;

Gracia, Javier ;

Benitez, Javier ;

van Asperen, Christi J. ;

Devilee, Peter .

JOURNAL OF MEDICAL GENETICS, 2012, 49 (10) :618-620

[8]

Jemal A, 2011, CA-CANCER J CLIN, V61, P134, DOI [10.3322/caac.20115, 10.3322/caac.21492, 10.3322/caac.20107]

[9] Mutation analysis of RAD51L1 (RAD51B/REC2) in multiple-case, non-BRCA1/2 breast cancer families [J].

Johnson, Julie ;

Healey, Sue ;

Khanna, Kum Kum ;

Chenevix-Trench, Georgia .

BREAST CANCER RESEARCH AND TREATMENT, 2011, 129 (01) :255-263

[10] Template-based protein structure modeling using the RaptorX web server [J].

Kaellberg, Morten ;

Wang, Haipeng ;

Wang, Sheng ;

Peng, Jian ;

Wang, Zhiyong ;

Lu, Hui ;

Xu, Jinbo .

NATURE PROTOCOLS, 2012, 7 (08) :1511-1522

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