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

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

doi:10.1093/carcin/bgt404

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

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

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Abstract

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.

Original language	English
Pages (from-to)	1012-1019
Journal	Carcinogenesis
Volume	35
Issue number	5
DOIs	https://doi.org/10.1093/carcin/bgt404
Publication status	Published - 2014

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Cancer and Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/carcin/bgt404

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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

@article{d2ef36e59e2447a398ce10aa022ada54,

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

abstract = "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.",

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

year = "2014",

doi = "10.1093/carcin/bgt404",

language = "English",

volume = "35",

pages = "1012--1019",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

number = "5",

}

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

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

SN - 0143-3334

VL - 35

SP - 1012

EP - 1019

JO - Carcinogenesis

JF - Carcinogenesis

IS - 5

ER -

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

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