Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

被引：34

作者：

Blanco, Ignacio ^{[1
]}

Kuchenbaecker, Karoline ^{[2
]}

Cuadras, Daniel ^{[3
]}

Wang, Xianshu ^{[4
]}

Barrowdale, Daniel ^{[2
]}

Ruiz de Garibay, Gorka ^{[5
]}

Librado, Pablo ^{[6
]}

Sanchez-Gracia, Alejandro ^{[6
]}

Rozas, Julio ^{[6
]}

Bonifaci, Nuria ^{[5
]}

McGuffog, Lesley ^{[2
]}

Pankratz, Vernon S. ^{[7
]}

Islam, Abul ^{[8
]}

Mateo, Francesca ^{[5
]}

Berenguer, Antoni ^{[3
]}

Petit, Anna ^{[9
]}

Catala, Isabel ^{[9
]}

Brunet, Joan ^{[10
]}

Feliubadalo, Lidia ^{[1
]}

Tornero, Eva ^{[1
]}

Benitez, Javier ^{[11
,12
]}

Osorio, Ana ^{[11
,12
]}

Cajal, Teresa Ramon Y. ^{[13
]}

Nevanlinna, Heli ^{[14
,15
]}

Aittomaki, Kristiina ^{[16
]}

Arun, Banu K. ^{[17
]}

Toland, Amanda E. ^{[18
]}

Karlan, Beth Y. ^{[19
]}

Walsh, Christine ^{[19
]}

Lester, Jenny ^{[19
]}

Greene, Mark H. ^{[20
]}

Mai, Phuong L. ^{[20
]}

Nussbaum, Robert L. ^{[21
]}

Andrulis, Irene L. ^{[22
,23
,24
]}

Domchek, Susan M. ^{[25
,26
]}

Nathanson, Katherine L. ^{[25
,26
]}

Rebbeck, Timothy R. ^{[27
,28
]}

Barkardottir, Rosa B. ^{[29
,30
]}

Jakubowska, Anna ^{[31
]}

Lubinski, Jan ^{[31
]}

Durda, Katarzyna ^{[31
]}

Jaworska-Bieniek, Katarzyna ^{[31
]}

Claes, Kathleen ^{[32
]}

Van Maerken, Tom ^{[32
]}

Diez, Orland ^{[33
,34
]}

Hansen, Thomas V. ^{[35
]}

Jonson, Lars ^{[35
]}

Gerdes, Anne-Marie ^{[36
]}

Ejlertsen, Bent ^{[37
]}

de la Hoya, Miguel ^{[38
]}

机构：

[1] Bellvitge Inst Biomed Res IDIBELL, Hereditary Canc Program, Catalan Inst Oncol ICO, Lhospitalet Del Llobrega, Catalonia, Spain

[2] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Epidemiol Study Familial Breast Canc,Ctr Canc Gen, Cambridge, England

[3] Bellvitge Inst Biomed Res IDIBELL, Stat Unit, Lhospitalet Del Llobrega, Catalonia, Spain

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

[5] Bellvitge Inst Biomed Res IDIBELL, Breast Canc & Syst Biol Unit, Catalan Inst Oncol ICO, Lhospitalet Del Llobrega, Catalonia, Spain

[6] Univ Barcelona, Dept Genet & Biodivers Res Inst IRBio, Barcelona, Catalonia, Spain

[7] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA

[8] Univ Dhaka, Dept Genet Engn & Biotechnol, Dhaka 1000, Bangladesh

[9] Bellvitge Inst Biomed Res IDIBELL, Univ Hosp Bellvitge, Dept Pathol, Lhospitalet Del Llobrega, Catalonia, Spain

[10] Hosp Josep Trueta, Girona Biomed Res Inst IDIBGI, Hereditary Canc Program, Catalan Inst Oncol ICO, Girona, Catalonia, Spain

[11] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain

[12] Biomed Network Rare Dis, Madrid, Spain

[13] Hosp Santa Creu & Sant Pau, Oncol Serv, Barcelona, Catalonia, Spain

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

[15] Univ Helsinki, Cent Hosp, Helsinki, Finland

[16] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland

[17] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA

[18] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med & Mol Virol Immunol & Med Genet, Div Human Canc Genet, Columbus, OH 43210 USA

[19] Cedars Sinai Med Ctr, Ctr Comprehens Canc, Womens Canc Program Samuel Oschin, Los Angeles, CA 90048 USA

[20] Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD USA

[21] Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA

[22] Univ Toronto, Samuel Lunenfeld Res Inst, Mt Sinai Hosp, Toronto, ON, Canada

[23] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[24] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[25] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[26] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

[27] Univ Penn Perelman, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[28] Univ Penn Perelman, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA

[29] Univ Iceland, Dept Pathol, Landspitali Univ Hosp, Reykjavik, Iceland

[30] Univ Iceland, Fac Med, BMC, Reykjavik, Iceland

[31] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland

[32] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium

[33] Vall Hebron Res Inst VHIR, Vall Hebron Inst Oncol, Oncogenet Grp, Barcelona, Catalonia, Spain

[34] Univ Autonoma Barcelona, E-08193 Barcelona, Catalonia, Spain

[35] Copenhagen Univ Hosp, Ctr Genom Med, Rigshosp, Copenhagen, Denmark

[36] Copenhagen Univ Hosp, Rigshosp, Dept Clin Genet, Copenhagen, Denmark

[37] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark

[38] San Carlos Res Inst IdISSC, Mol Oncol Lab, Hosp Clin San Carlos, Madrid, Spain

[39] Glan Clwyd Gen Hosp, All Wales Med Genet Serv, Rhyl, Wales

[40] Singleton Hosp, All Wales Med Genet Serv, Swansea SA2 8QA, W Glam, Wales

[41] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Clin Genet, London, England

[42] Cent Manchester Univ Hosp Natl Hlth Serv NHS Fdn, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England

[43] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England

[44] Kennedy Galton Ctr, North West Thames Reg Genet Serv, Harrow, Middx, England

[45] Addenbrookes Hosp, Dept Clin Genet, East Anglian Reg Genet Serv, Cambridge, England

[46] Birmingham Womens Hosp Healthcare Natl Hlth Serv, West Midlands Reg Genet Serv, Birmingham, W Midlands, England

[47] Univ Porto, Dept Genet, Portuguese Oncol Inst, P-4100 Porto, Portugal

[48] Univ Porto, Biomed Sci Inst ICBAS, P-4100 Porto, Portugal

[49] Netherlands Canc Inst NKI, Hereditary Breast & Ovarian Canc Res Grp Netherla, Amsterdam, Netherlands

[50] Netherlands Canc Inst NKI, Family Canc Clin, Amsterdam, Netherlands

来源：

PLOS ONE | 2015年 / 10卷 / 04期

基金：

美国国家卫生研究院; 芬兰科学院; 澳大利亚国家健康与医学研究理事会; 加拿大健康研究院; 英国医学研究理事会;

关键词：

GENE-EXPRESSION SIGNATURE; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; POLYMORPHISM; MODIFIERS;

D O I：

10.1371/journal.pone.0120020

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：

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

引用

页数：18

共 43 条

[1] An integrated map of genetic variation from 1,092 human genomes [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Schmidt, Jeanette P. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

Wang, Min ;

Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Li, Zhuo ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Su, Zhe ;

Tai, Shuaishuai ;

Tang, Meifang .

NATURE, 2012, 491 (7422) :56-65

[2] 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 [J].

Antoniou, Antonis C. ;

Wang, Xianshu ;

Fredericksen, Zachary S. ;

McGuffog, Lesley ;

Tarrell, Robert ;

Sinilnikova, Olga M. ;

Healey, Sue ;

Morrison, Jonathan ;

Kartsonaki, Christiana ;

Lesnick, Timothy ;

Ghoussaini, Maya ;

Barrowdale, Daniel ;

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, Dominique ;

Houdayer, Claude ;

Mazoyer, Sylvie ;

Giraud, Sophie ;

Lasset, Christine ;

Remenieras, Audrey ;

Caron, Olivier ;

Hardouin, Agnes ;

Berthet, Pascaline ;

Hogervorst, Frans B. L. ;

Rookus, Matti A. ;

Jager, Agnes ;

van den Ouweland, Ans ;

Hoogerbrugge, Nicoline ;

van der Luijt, Rob B. ;

Meijers-Heijboer, Hanne ;

Garcia, Encarna B. Gomez ;

Devilee, Peter ;

Vreeswijk, Maaike P. G. ;

Lubinski, Jan ;

Jakubowska, Anna ;

Gronwald, Jacek ;

Huzarski, Tomasz ;

Byrski, Tomasz ;

Gorski, Bohdan ;

Cybulski, Cezary ;

Spurdle, Amanda B. .

NATURE GENETICS, 2010, 42 (10) :885-+

[3] Evaluation of Association Methods for Analysing Modifiers of Disease Risk in Carriers of High-Risk Mutations [J].

Barnes, Daniel R. ;

Lee, Andrew ;

Easton, Douglas F. ;

Antoniou, Antonis C. .

GENETIC EPIDEMIOLOGY, 2012, 36 (03) :274-291

[4] Integrating gene expression and epidemiological data for the discovery of genetic interactions associated with cancer risk [J].

Bonifaci, Nuria ;

Colas, Eva ;

Serra-Musach, Jordi ;

Karbalai, Nazanin ;

Brunet, Joan ;

Gomez, Antonio ;

Esteller, Manel ;

Fernandez-Taboada, Enrique ;

Berenguer, Antoni ;

Reventos, Jaume ;

Mueller-Myhsok, Bertram ;

Amundadottir, Laufey ;

Duell, Eric J. ;

Angel Pujana, Miquel .

CARCINOGENESIS, 2014, 35 (03) :578-585

[5] Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival [J].

Chang, HY ;

Nuyten, DSA ;

Sneddon, JB ;

Hastie, T ;

Tibshirani, R ;

Sorlie, T ;

Dai, HY ;

He, YDD ;

van't Veer, LJ ;

Bartelink, H ;

van de Rijn, M ;

Brown, PO ;

van de Vijver, MJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (10) :3738-3743

[6] Extreme Evolutionary Disparities Seen in Positive Selection across Seven Complex Diseases [J].

Corona, Erik ;

Dudley, Joel T. ;

Butte, Atul J. .

PLOS ONE, 2010, 5 (08)

[7] The Genetic Landscape of a Cell [J].

Costanzo, Michael ;

Baryshnikova, Anastasia ;

Bellay, Jeremy ;

Kim, Yungil ;

Spear, Eric D. ;

Sevier, Carolyn S. ;

Ding, Huiming ;

Koh, Judice L. Y. ;

Toufighi, Kiana ;

Mostafavi, Sara ;

Prinz, Jeany ;

Onge, Robert P. St. ;

VanderSluis, Benjamin ;

Makhnevych, Taras ;

Vizeacoumar, Franco J. ;

Alizadeh, Solmaz ;

Bahr, Sondra ;

Brost, Renee L. ;

Chen, Yiqun ;

Cokol, Murat ;

Deshpande, Raamesh ;

Li, Zhijian ;

Lin, Zhen-Yuan ;

Liang, Wendy ;

Marback, Michaela ;

Paw, Jadine ;

Luis, Bryan-Joseph San ;

Shuteriqi, Ermira ;

Tong, Amy Hin Yan ;

van Dyk, Nydia ;

Wallace, Iain M. ;

Whitney, Joseph A. ;

Weirauch, Matthew T. ;

Zhong, Guoqing ;

Zhu, Hongwei ;

Houry, Walid A. ;

Brudno, Michael ;

Ragibizadeh, Sasan ;

Papp, Balazs ;

Pal, Csaba ;

Roth, Frederick P. ;

Giaever, Guri ;

Nislow, Corey ;

Troyanskaya, Olga G. ;

Bussey, Howard ;

Bader, Gary D. ;

Gingras, Anne-Claude ;

Morris, Quaid D. ;

Kim, Philip M. ;

Kaiser, Chris A. .

SCIENCE, 2010, 327 (5964) :425-431

[8] AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers:: A consortium of investigators of modifiers of BRCA1/2 study [J].

Couch, Fergus J. ;

Sinilnikova, Olga ;

Vierkant, Robert A. ;

Pankratz, V. Shane ;

Fredericksen, Zachary S. ;

Stoppa-Lyonnet, Dominique ;

Coupier, Isabelle ;

Hughes, David ;

Hardouin, Agnes ;

Berthet, Pascaline ;

Peock, Susan ;

Cook, Margaret ;

Baynes, Caroline ;

Hodgson, Shirley ;

Morrison, Patrick J. ;

Porteous, Mary E. ;

Jakubowska, Anna ;

Lubinski, Jan ;

Gronwald, Jacek ;

Spurdle, Amanda B. ;

kConFab ;

Schmutzler, Rita ;

Versmold, Beatrix ;

Engel, Christoph ;

Meindl, Alfons ;

Sutter, Christian ;

Horst, Jurgen ;

Schaefer, Dieter ;

Offit, Kenneth ;

Kirchhoff, Tomas ;

Andrulis, Irene L. ;

Ilyushik, Eduard ;

Glendon, Gordon ;

Devilee, Peter ;

Vreeswijk, Maaike P. G. ;

Vasen, Hans F. A. ;

Borg, Ake ;

Backenhorn, Katja ;

Struewing, Jeffery P. ;

Greene, Mark H. ;

Neuhausen, Susan L. ;

Rebbeck, Timothy R. ;

Nathanson, Katherine ;

Domchek, Susan ;

Wagner, Theresa ;

Garber, Judy E. ;

Szabo, Csilla ;

Zikan, Michal ;

Foretova, Lenka ;

Olson, Janet E. .

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2007, 16 (07) :1416-1421

[9] 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)

[10] Systematic Mapping of Genetic Interaction Networks [J].

Dixon, Scott J. ;

Costanzo, Michael ;

Baryshnikova, Anastasia ;

Andrews, Brenda ;

Boone, Charles .

ANNUAL REVIEW OF GENETICS, 2009, 43 :601-625

← 1 2 3 4 5 →