Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

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Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. / Purrington, Kristen S.; Slager, Susan; Eccles, Diana; Yannoukakos, Drakoulis; Fasching, Peter A.; Miron, Penelope; Carpenter, Jane; Chang-Claude, Jenny; Martin, Nicholas G.; Montgomery, Grant W.; Kristensen, Vessela; Anton-Culver, Hoda; Goodfellow, Paul; Tapper, William J.; Rafiq, Sajjad; Gerty, Susan M.; Durcan, Lorraine; Konstantopoulou, Irene; Fostira, Florentia; Vratimos, Athanassios; Apostolou, Paraskevi; Konstanta, Irene; Kotoula, Vassiliki; Lakis, Sotiris; Dimopoulos, Meletios A.; Skarlos, Dimosthenis; Pectasides, Dimitrios; Fountzilas, George; Beckmann, Matthias W.; Hein, Alexander; Ruebner, Matthias; Ekici, Arif B.; Hartmann, Arndt; Schulz-Wendtland, Ruediger; Renner, Stefan P.; Janni, Wolfgang; Rack, Brigitte; Scholz, Christoph; Neugebauer, Julia; Andergassen, Ulrich; Lux, Michael P.; Haeberle, Lothar; Clarke, Christine; Pathmanathan, Nirmala; Rudolph, Anja; Flesch-Janys, Dieter; Nickels, Stefan; Olson, Janet E.; Ingle, James N.; Olswold, Curtis; Slettedahl, Seth; Eckel-Passow, Jeanette E.; Anderson, S. Keith; Visscher, Daniel W.; Cafourek, Victoria L.; Sicotte, Hugues; Prodduturi, Naresh; Weiderpass, Elisabete; Bernstein, Leslie; Ziogas, Argyrios; Ivanovich, Jennifer; Giles, Graham G.; Baglietto, Laura; Southey, Melissa; Kosma, Veli-Matti; Fischer, Hans-Peter; Reed, Malcom W. R.; Cross, Simon S.; Deming-Halverson, Sandra; Shrubsole, Martha; Cai, Qiuyin; Shu, Xiao-Ou; Daly, Mary; Weaver, JoEllen; Ross, Eric; Klemp, Jennifer; Sharma, Priyanka; Torres, Diana; Rudiger, Thomas; Wolfing, Heidrun; Ulmer, Hans-Ulrich; Försti, Asta; Khoury, Thaer; Kumar, Shicha; Pilarski, Robert; Shapiro, Charles L.; Greco, Dario; Heikkila, Paivi; Aittomaki, Kristiina; Blomqvist, Carl; Irwanto, Astrid; Liu, Jianjun; Pankratz, Vernon Shane; Wang, Xianshu; Severi, Gianluca; Mannermaa, Arto; Easton, Douglas; Hall, Per; Brauch, Hiltrud; Cox, Angela; Zheng, Wei; Godwin, Andrew K.; Hamann, Ute; Ambrosone, Christine; Toland, Amanda Ewart; Nevanlinna, Heli; Vachon, Celine M.; Couch, Fergus J.

In: Carcinogenesis, Vol. 35, No. 5, 2014, p. 1012-1019.

Research output: Contribution to journalArticle

Harvard

Purrington, KS, Slager, S, Eccles, D, Yannoukakos, D, Fasching, PA, Miron, P, Carpenter, J, Chang-Claude, J, Martin, NG, Montgomery, GW, Kristensen, V, Anton-Culver, H, Goodfellow, P, Tapper, WJ, Rafiq, S, Gerty, SM, Durcan, L, Konstantopoulou, I, Fostira, F, Vratimos, A, Apostolou, P, Konstanta, I, Kotoula, V, Lakis, S, Dimopoulos, MA, Skarlos, D, Pectasides, D, Fountzilas, G, Beckmann, MW, Hein, A, Ruebner, M, Ekici, AB, Hartmann, A, Schulz-Wendtland, R, Renner, SP, Janni, W, Rack, B, Scholz, C, Neugebauer, J, Andergassen, U, Lux, MP, Haeberle, L, Clarke, C, Pathmanathan, N, Rudolph, A, Flesch-Janys, D, Nickels, S, Olson, JE, Ingle, JN, Olswold, C, Slettedahl, S, Eckel-Passow, JE, Anderson, SK, Visscher, DW, Cafourek, VL, Sicotte, H, Prodduturi, N, Weiderpass, E, Bernstein, L, Ziogas, A, Ivanovich, J, Giles, GG, Baglietto, L, Southey, M, Kosma, V-M, Fischer, H-P, Reed, MWR, Cross, SS, Deming-Halverson, S, Shrubsole, M, Cai, Q, Shu, X-O, Daly, M, Weaver, J, Ross, E, Klemp, J, Sharma, P, Torres, D, Rudiger, T, Wolfing, H, Ulmer, H-U, Försti, A, Khoury, T, Kumar, S, Pilarski, R, Shapiro, CL, Greco, D, Heikkila, P, Aittomaki, K, Blomqvist, C, Irwanto, A, Liu, J, Pankratz, VS, Wang, X, Severi, G, Mannermaa, A, Easton, D, Hall, P, Brauch, H, Cox, A, Zheng, W, Godwin, AK, Hamann, U, Ambrosone, C, Toland, AE, Nevanlinna, H, Vachon, CM & Couch, FJ 2014, 'Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer', Carcinogenesis, vol. 35, no. 5, pp. 1012-1019. https://doi.org/10.1093/carcin/bgt404

APA

Purrington, K. S., Slager, S., Eccles, D., Yannoukakos, D., Fasching, P. A., Miron, P., Carpenter, J., Chang-Claude, J., Martin, N. G., Montgomery, G. W., Kristensen, V., Anton-Culver, H., Goodfellow, P., Tapper, W. J., Rafiq, S., Gerty, S. M., Durcan, L., Konstantopoulou, I., Fostira, F., ... Couch, F. J. (2014). Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. Carcinogenesis, 35(5), 1012-1019. https://doi.org/10.1093/carcin/bgt404

CBE

Purrington KS, Slager S, Eccles D, Yannoukakos D, Fasching PA, Miron P, Carpenter J, Chang-Claude J, Martin NG, Montgomery GW, Kristensen V, Anton-Culver H, Goodfellow P, Tapper WJ, Rafiq S, Gerty SM, Durcan L, Konstantopoulou I, Fostira F, Vratimos A, Apostolou P, Konstanta I, Kotoula V, Lakis S, Dimopoulos MA, Skarlos D, Pectasides D, Fountzilas G, Beckmann MW, Hein A, Ruebner M, Ekici AB, Hartmann A, Schulz-Wendtland R, Renner SP, Janni W, Rack B, Scholz C, Neugebauer J, Andergassen U, Lux MP, Haeberle L, Clarke C, Pathmanathan N, Rudolph A, Flesch-Janys D, Nickels S, Olson JE, Ingle JN, Olswold C, Slettedahl S, Eckel-Passow JE, Anderson SK, Visscher DW, Cafourek VL, Sicotte H, Prodduturi N, Weiderpass E, Bernstein L, Ziogas A, Ivanovich J, Giles GG, Baglietto L, Southey M, Kosma V-M, Fischer H-P, Reed MWR, Cross SS, Deming-Halverson S, Shrubsole M, Cai Q, Shu X-O, Daly M, Weaver J, Ross E, Klemp J, Sharma P, Torres D, Rudiger T, Wolfing H, Ulmer H-U, Försti A, Khoury T, Kumar S, Pilarski R, Shapiro CL, Greco D, Heikkila P, Aittomaki K, Blomqvist C, Irwanto A, Liu J, Pankratz VS, Wang X, Severi G, Mannermaa A, Easton D, Hall P, Brauch H, Cox A, Zheng W, Godwin AK, Hamann U, Ambrosone C, Toland AE, Nevanlinna H, Vachon CM, Couch FJ. 2014. Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. Carcinogenesis. 35(5):1012-1019. https://doi.org/10.1093/carcin/bgt404

MLA

Vancouver

Author

Purrington, Kristen S. ; Slager, Susan ; Eccles, Diana ; Yannoukakos, Drakoulis ; Fasching, Peter A. ; Miron, Penelope ; Carpenter, Jane ; Chang-Claude, Jenny ; Martin, Nicholas G. ; Montgomery, Grant W. ; Kristensen, Vessela ; Anton-Culver, Hoda ; Goodfellow, Paul ; Tapper, William J. ; Rafiq, Sajjad ; Gerty, Susan M. ; Durcan, Lorraine ; Konstantopoulou, Irene ; Fostira, Florentia ; Vratimos, Athanassios ; Apostolou, Paraskevi ; Konstanta, Irene ; Kotoula, Vassiliki ; Lakis, Sotiris ; Dimopoulos, Meletios A. ; Skarlos, Dimosthenis ; Pectasides, Dimitrios ; Fountzilas, George ; Beckmann, Matthias W. ; Hein, Alexander ; Ruebner, Matthias ; Ekici, Arif B. ; Hartmann, Arndt ; Schulz-Wendtland, Ruediger ; Renner, Stefan P. ; Janni, Wolfgang ; Rack, Brigitte ; Scholz, Christoph ; Neugebauer, Julia ; Andergassen, Ulrich ; Lux, Michael P. ; Haeberle, Lothar ; Clarke, Christine ; Pathmanathan, Nirmala ; Rudolph, Anja ; Flesch-Janys, Dieter ; Nickels, Stefan ; Olson, Janet E. ; Ingle, James N. ; Olswold, Curtis ; Slettedahl, Seth ; Eckel-Passow, Jeanette E. ; Anderson, S. Keith ; Visscher, Daniel W. ; Cafourek, Victoria L. ; Sicotte, Hugues ; Prodduturi, Naresh ; Weiderpass, Elisabete ; Bernstein, Leslie ; Ziogas, Argyrios ; Ivanovich, Jennifer ; Giles, Graham G. ; Baglietto, Laura ; Southey, Melissa ; Kosma, Veli-Matti ; Fischer, Hans-Peter ; Reed, Malcom W. R. ; Cross, Simon S. ; Deming-Halverson, Sandra ; Shrubsole, Martha ; Cai, Qiuyin ; Shu, Xiao-Ou ; Daly, Mary ; Weaver, JoEllen ; Ross, Eric ; Klemp, Jennifer ; Sharma, Priyanka ; Torres, Diana ; Rudiger, Thomas ; Wolfing, Heidrun ; Ulmer, Hans-Ulrich ; Försti, Asta ; Khoury, Thaer ; Kumar, Shicha ; Pilarski, Robert ; Shapiro, Charles L. ; Greco, Dario ; Heikkila, Paivi ; Aittomaki, Kristiina ; Blomqvist, Carl ; Irwanto, Astrid ; Liu, Jianjun ; Pankratz, Vernon Shane ; Wang, Xianshu ; Severi, Gianluca ; Mannermaa, Arto ; Easton, Douglas ; Hall, Per ; Brauch, Hiltrud ; Cox, Angela ; Zheng, Wei ; Godwin, Andrew K. ; Hamann, Ute ; Ambrosone, Christine ; Toland, Amanda Ewart ; Nevanlinna, Heli ; Vachon, Celine M. ; Couch, Fergus J. / Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. In: Carcinogenesis. 2014 ; Vol. 35, No. 5. pp. 1012-1019.

RIS

TY - JOUR

T1 - Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

AU - Purrington, Kristen S.

AU - Slager, Susan

AU - Eccles, Diana

AU - Yannoukakos, Drakoulis

AU - Fasching, Peter A.

AU - Miron, Penelope

AU - Carpenter, Jane

AU - Chang-Claude, Jenny

AU - Martin, Nicholas G.

AU - Montgomery, Grant W.

AU - Kristensen, Vessela

AU - Anton-Culver, Hoda

AU - Goodfellow, Paul

AU - Tapper, William J.

AU - Rafiq, Sajjad

AU - Gerty, Susan M.

AU - Durcan, Lorraine

AU - Konstantopoulou, Irene

AU - Fostira, Florentia

AU - Vratimos, Athanassios

AU - Apostolou, Paraskevi

AU - Konstanta, Irene

AU - Kotoula, Vassiliki

AU - Lakis, Sotiris

AU - Dimopoulos, Meletios A.

AU - Skarlos, Dimosthenis

AU - Pectasides, Dimitrios

AU - Fountzilas, George

AU - Beckmann, Matthias W.

AU - Hein, Alexander

AU - Ruebner, Matthias

AU - Ekici, Arif B.

AU - Hartmann, Arndt

AU - Schulz-Wendtland, Ruediger

AU - Renner, Stefan P.

AU - Janni, Wolfgang

AU - Rack, Brigitte

AU - Scholz, Christoph

AU - Neugebauer, Julia

AU - Andergassen, Ulrich

AU - Lux, Michael P.

AU - Haeberle, Lothar

AU - Clarke, Christine

AU - Pathmanathan, Nirmala

AU - Rudolph, Anja

AU - Flesch-Janys, Dieter

AU - Nickels, Stefan

AU - Olson, Janet E.

AU - Ingle, James N.

AU - Olswold, Curtis

AU - Slettedahl, Seth

AU - Eckel-Passow, Jeanette E.

AU - Anderson, S. Keith

AU - Visscher, Daniel W.

AU - Cafourek, Victoria L.

AU - Sicotte, Hugues

AU - Prodduturi, Naresh

AU - Weiderpass, Elisabete

AU - Bernstein, Leslie

AU - Ziogas, Argyrios

AU - Ivanovich, Jennifer

AU - Giles, Graham G.

AU - Baglietto, Laura

AU - Southey, Melissa

AU - Kosma, Veli-Matti

AU - Fischer, Hans-Peter

AU - Reed, Malcom W. R.

AU - Cross, Simon S.

AU - Deming-Halverson, Sandra

AU - Shrubsole, Martha

AU - Cai, Qiuyin

AU - Shu, Xiao-Ou

AU - Daly, Mary

AU - Weaver, JoEllen

AU - Ross, Eric

AU - Klemp, Jennifer

AU - Sharma, Priyanka

AU - Torres, Diana

AU - Rudiger, Thomas

AU - Wolfing, Heidrun

AU - Ulmer, Hans-Ulrich

AU - Försti, Asta

AU - Khoury, Thaer

AU - Kumar, Shicha

AU - Pilarski, Robert

AU - Shapiro, Charles L.

AU - Greco, Dario

AU - Heikkila, Paivi

AU - Aittomaki, Kristiina

AU - Blomqvist, Carl

AU - Irwanto, Astrid

AU - Liu, Jianjun

AU - Pankratz, Vernon Shane

AU - Wang, Xianshu

AU - Severi, Gianluca

AU - Mannermaa, Arto

AU - Easton, Douglas

AU - Hall, Per

AU - Brauch, Hiltrud

AU - Cox, Angela

AU - Zheng, Wei

AU - Godwin, Andrew K.

AU - Hamann, Ute

AU - Ambrosone, Christine

AU - Toland, Amanda Ewart

AU - Nevanlinna, Heli

AU - Vachon, Celine M.

AU - Couch, Fergus J.

PY - 2014

Y1 - 2014

N2 - In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.

AB - In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.

U2 - 10.1093/carcin/bgt404

DO - 10.1093/carcin/bgt404

M3 - Article

C2 - 24325915

VL - 35

SP - 1012

EP - 1019

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 5

ER -