19p13.1 Is a Triple-Negative-Specific Breast Cancer Susceptibility Locus

KN Stevens; Z Fredericksen; CM Vachon; XS Wang; S Margolin; A Lindblom; H Nevanlinna; D Greco; K Aittomaki; C Blomqvist; J Chang-Claude; A Vrieling; D Flesch-Janys; HP Sinn; S Wang-Gohrke; S Nickels; H Brauch; YD Ko; HP Fischer; RK Schmutzler; A Meindl; CR Bartram; S Schott; C Engel; AK Godwin; J Weaver; HB Pathak; P Sharma; H Brenner; H Muller; V Arndt; C Stegmaier; P Miron; D Yannoukakos; A Stavropoulou; G Fountzilas; HJ Gogas; R Swann; M Dwek; A Perkins; RL Milne; J Benitez; MP Zamora; JIA Perez; SE Bojesen; SF Nielsen; BG Nordestgaard; H Flyger; P Guenel; F Menegaux; E Cordina-Duverger; B Burwinkel; F Marme; A Schneeweiss; C Sohn; E Sawyer; I Tomlinson; MJ Kerin; J Peto; N Johnson; O Fletcher; ID Silva; PA Fasching; MW Beckmann; A Hartmann; AB Ekici; A Lophatananon; K Muir; P Puttawibul; S Wiangnon; Marjanka K Schmidt; A Broeks; LM Braaf; EH Rosenberg; JL Hopper; C Apicella; DJ Park; MC Southey; AJ Swerdlow; A Ashworth; N Orr; MJ Schoemaker; H Anton-Culver; A Ziogas; L Bernstein; CC Dur; CY Shen; JC Yu; HM Hsu; CN Hsiung; U Hamann; T Dunnebier; T Rudiger; HU Ulmer; PP Pharoah; AM Dunning; MK Humphreys; Q (Qing) Wang; A Cox; SS Cross; MW Reed; P Hall; K Czene; CB Ambrosone; F Ademuyiwa; H Hwang; DM Eccles; M Garcia-Closas; JD Figueroa; ME Sherman; J Lissowska; P Devilee; Caroline Seynaeve; RAEM Tollenaar; Maartje Hooning; IL Andrulis; JA Knight; G Glendon; AM Mulligan; R Winqvist; K Pylkas; A Jukkola-Vuorinen; M Grip; EM John; A Miron; GG Alnaes; V Kristensen; AL Borresen-Dale; GG Giles; L Baglietto; CA McLean; G Severi; ML Kosel; VS Pankratz; S Slager; JE Olson; P Radice; P Peterlongo; S Manoukian; M Barile; D Lambrechts; S Hatse; AS Dieudonne; MR Christiaens; G Chenevix-Trench; J Beesley; XQ Chen; A Mannermaa; VM Kosma; JM Hartikainen; Y Soini; DF Easton; FJ Couch; T Truong

doi:10.1158/0008-5472.CAN-11-3364

19p13.1 Is a Triple-Negative-Specific Breast Cancer Susceptibility Locus

KN Stevens, Z Fredericksen, CM Vachon, XS Wang, S Margolin, A Lindblom, H Nevanlinna, D Greco, K Aittomaki, C Blomqvist, J Chang-Claude, A Vrieling, D Flesch-Janys, HP Sinn, S Wang-Gohrke, S Nickels, H Brauch, YD Ko, HP Fischer, RK SchmutzlerA Meindl, CR Bartram, S Schott, C Engel, AK Godwin, J Weaver, HB Pathak, P Sharma, H Brenner, H Muller, V Arndt, C Stegmaier, P Miron, D Yannoukakos, A Stavropoulou, G Fountzilas, HJ Gogas, R Swann, M Dwek, A Perkins, RL Milne, J Benitez, MP Zamora, JIA Perez, SE Bojesen, SF Nielsen, BG Nordestgaard, H Flyger, P Guenel, F Menegaux, E Cordina-Duverger, B Burwinkel, F Marme, A Schneeweiss, C Sohn, E Sawyer, I Tomlinson, MJ Kerin, J Peto, N Johnson, O Fletcher, ID Silva, PA Fasching, MW Beckmann, A Hartmann, AB Ekici, A Lophatananon, K Muir, P Puttawibul, S Wiangnon, Marjanka K Schmidt, A Broeks, LM Braaf, EH Rosenberg, JL Hopper, C Apicella, DJ Park, MC Southey, AJ Swerdlow, A Ashworth, N Orr, MJ Schoemaker, H Anton-Culver, A Ziogas, L Bernstein, CC Dur, CY Shen, JC Yu, HM Hsu, CN Hsiung, U Hamann, T Dunnebier, T Rudiger, HU Ulmer, PP Pharoah, AM Dunning, MK Humphreys, Q (Qing) Wang, A Cox, SS Cross, MW Reed, P Hall, K Czene, CB Ambrosone, F Ademuyiwa, H Hwang, DM Eccles, M Garcia-Closas, JD Figueroa, ME Sherman, J Lissowska, P Devilee, Caroline Seynaeve, RAEM Tollenaar, Maartje Hooning, IL Andrulis, JA Knight, G Glendon, AM Mulligan, R Winqvist, K Pylkas, A Jukkola-Vuorinen, M Grip, EM John, A Miron, GG Alnaes, V Kristensen, AL Borresen-Dale, GG Giles, L Baglietto, CA McLean, G Severi, ML Kosel, VS Pankratz, S Slager, JE Olson, P Radice, P Peterlongo, S Manoukian, M Barile, D Lambrechts, S Hatse, AS Dieudonne, MR Christiaens, G Chenevix-Trench, J Beesley, XQ Chen, A Mannermaa, VM Kosma, JM Hartikainen, Y Soini, DF Easton, FJ Couch, T Truong

Research output: Contribution to journal › Article › Academic › peer-review

81 Citations (Scopus)

Abstract

The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 x 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 x 10(-7)). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18-1.33; P = 3.31 x 10-(13)]. Thus, 19p13.1 is the first triple-negativespecific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795-803. (C)2012 AACR.

Original language	Undefined/Unknown
Pages (from-to)	1795-1803
Number of pages	9
Journal	Cancer Research
Volume	72
Issue number	7
DOIs	https://doi.org/10.1158/0008-5472.CAN-11-3364
Publication status	Published - 2012

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10.1158/0008-5472.CAN-11-3364

http://hdl.handle.net/1765/69575

Cite this

Stevens, KN., Fredericksen, Z., Vachon, CM., Wang, XS., Margolin, S., Lindblom, A., Nevanlinna, H., Greco, D., Aittomaki, K., Blomqvist, C., Chang-Claude, J., Vrieling, A., Flesch-Janys, D., Sinn, HP., Wang-Gohrke, S., Nickels, S., Brauch, H., Ko, YD., Fischer, HP., ... Truong, T. (2012). 19p13.1 Is a Triple-Negative-Specific Breast Cancer Susceptibility Locus. Cancer Research, 72(7), 1795-1803. https://doi.org/10.1158/0008-5472.CAN-11-3364

@article{66e4a029d45240d5ba3a3e90ce83a261,

title = "19p13.1 Is a Triple-Negative-Specific Breast Cancer Susceptibility Locus",

abstract = "The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 x 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 x 10(-7)). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18-1.33; P = 3.31 x 10-(13)]. Thus, 19p13.1 is the first triple-negativespecific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795-803. (C)2012 AACR.",

author = "KN Stevens and Z Fredericksen and CM Vachon and XS Wang and S Margolin and A Lindblom and H Nevanlinna and D Greco and K Aittomaki and C Blomqvist and J Chang-Claude and A Vrieling and D Flesch-Janys and HP Sinn and S Wang-Gohrke and S Nickels and H Brauch and YD Ko and HP Fischer and RK Schmutzler and A Meindl and CR Bartram and S Schott and C Engel and AK Godwin and J Weaver and HB Pathak and P Sharma and H Brenner and H Muller and V Arndt and C Stegmaier and P Miron and D Yannoukakos and A Stavropoulou and G Fountzilas and HJ Gogas and R Swann and M Dwek and A Perkins and RL Milne and J Benitez and MP Zamora and JIA Perez and SE Bojesen and SF Nielsen and BG Nordestgaard and H Flyger and P Guenel and F Menegaux and E Cordina-Duverger and B Burwinkel and F Marme and A Schneeweiss and C Sohn and E Sawyer and I Tomlinson and MJ Kerin and J Peto and N Johnson and O Fletcher and ID Silva and PA Fasching and MW Beckmann and A Hartmann and AB Ekici and A Lophatananon and K Muir and P Puttawibul and S Wiangnon and Schmidt, {Marjanka K} and A Broeks and LM Braaf and EH Rosenberg and JL Hopper and C Apicella and DJ Park and MC Southey and AJ Swerdlow and A Ashworth and N Orr and MJ Schoemaker and H Anton-Culver and A Ziogas and L Bernstein and CC Dur and CY Shen and JC Yu and HM Hsu and CN Hsiung and U Hamann and T Dunnebier and T Rudiger and HU Ulmer and PP Pharoah and AM Dunning and MK Humphreys and Wang, {Q (Qing)} and A Cox and SS Cross and MW Reed and P Hall and K Czene and CB Ambrosone and F Ademuyiwa and H Hwang and DM Eccles and M Garcia-Closas and JD Figueroa and ME Sherman and J Lissowska and P Devilee and Caroline Seynaeve and RAEM Tollenaar and Maartje Hooning and IL Andrulis and JA Knight and G Glendon and AM Mulligan and R Winqvist and K Pylkas and A Jukkola-Vuorinen and M Grip and EM John and A Miron and GG Alnaes and V Kristensen and AL Borresen-Dale and GG Giles and L Baglietto and CA McLean and G Severi and ML Kosel and VS Pankratz and S Slager and JE Olson and P Radice and P Peterlongo and S Manoukian and M Barile and D Lambrechts and S Hatse and AS Dieudonne and MR Christiaens and G Chenevix-Trench and J Beesley and XQ Chen and A Mannermaa and VM Kosma and JM Hartikainen and Y Soini and DF Easton and FJ Couch and T Truong",

year = "2012",

doi = "10.1158/0008-5472.CAN-11-3364",

language = "Undefined/Unknown",

volume = "72",

pages = "1795--1803",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

number = "7",

}

Stevens, KN, Fredericksen, Z, Vachon, CM, Wang, XS, Margolin, S, Lindblom, A, Nevanlinna, H, Greco, D, Aittomaki, K, Blomqvist, C, Chang-Claude, J, Vrieling, A, Flesch-Janys, D, Sinn, HP, Wang-Gohrke, S, Nickels, S, Brauch, H, Ko, YD, Fischer, HP, Schmutzler, RK, Meindl, A, Bartram, CR, Schott, S, Engel, C, Godwin, AK, Weaver, J, Pathak, HB, Sharma, P, Brenner, H, Muller, H, Arndt, V, Stegmaier, C, Miron, P, Yannoukakos, D, Stavropoulou, A, Fountzilas, G, Gogas, HJ, Swann, R, Dwek, M, Perkins, A, Milne, RL, Benitez, J, Zamora, MP, Perez, JIA, Bojesen, SE, Nielsen, SF, Nordestgaard, BG, Flyger, H, Guenel, P, Menegaux, F, Cordina-Duverger, E, Burwinkel, B, Marme, F, Schneeweiss, A, Sohn, C, Sawyer, E, Tomlinson, I, Kerin, MJ, Peto, J, Johnson, N, Fletcher, O, Silva, ID, Fasching, PA, Beckmann, MW, Hartmann, A, Ekici, AB, Lophatananon, A, Muir, K, Puttawibul, P, Wiangnon, S, Schmidt, MK, Broeks, A, Braaf, LM, Rosenberg, EH, Hopper, JL, Apicella, C, Park, DJ, Southey, MC, Swerdlow, AJ, Ashworth, A, Orr, N, Schoemaker, MJ, Anton-Culver, H, Ziogas, A, Bernstein, L, Dur, CC, Shen, CY, Yu, JC, Hsu, HM, Hsiung, CN, Hamann, U, Dunnebier, T, Rudiger, T, Ulmer, HU, Pharoah, PP, Dunning, AM, Humphreys, MK, Wang, Q, Cox, A, Cross, SS, Reed, MW, Hall, P, Czene, K, Ambrosone, CB, Ademuyiwa, F, Hwang, H, Eccles, DM, Garcia-Closas, M, Figueroa, JD, Sherman, ME, Lissowska, J, Devilee, P, Seynaeve, C, Tollenaar, RAEM, Hooning, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, John, EM, Miron, A, Alnaes, GG, Kristensen, V, Borresen-Dale, AL, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Kosel, ML, Pankratz, VS, Slager, S, Olson, JE, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Lambrechts, D, Hatse, S, Dieudonne, AS, Christiaens, MR, Chenevix-Trench, G, Beesley, J, Chen, XQ, Mannermaa, A, Kosma, VM, Hartikainen, JM, Soini, Y, Easton, DF, Couch, FJ & Truong, T 2012, '19p13.1 Is a Triple-Negative-Specific Breast Cancer Susceptibility Locus', Cancer Research, vol. 72, no. 7, pp. 1795-1803. https://doi.org/10.1158/0008-5472.CAN-11-3364

TY - JOUR

T1 - 19p13.1 Is a Triple-Negative-Specific Breast Cancer Susceptibility Locus

AU - Stevens, KN

AU - Fredericksen, Z

AU - Vachon, CM

AU - Wang, XS

AU - Margolin, S

AU - Lindblom, A

AU - Nevanlinna, H

AU - Greco, D

AU - Aittomaki, K

AU - Blomqvist, C

AU - Chang-Claude, J

AU - Vrieling, A

AU - Flesch-Janys, D

AU - Sinn, HP

AU - Wang-Gohrke, S

AU - Nickels, S

AU - Brauch, H

AU - Ko, YD

AU - Fischer, HP

AU - Schmutzler, RK

AU - Meindl, A

AU - Bartram, CR

AU - Schott, S

AU - Engel, C

AU - Godwin, AK

AU - Weaver, J

AU - Pathak, HB

AU - Sharma, P

AU - Brenner, H

AU - Muller, H

AU - Arndt, V

AU - Stegmaier, C

AU - Miron, P

AU - Yannoukakos, D

AU - Stavropoulou, A

AU - Fountzilas, G

AU - Gogas, HJ

AU - Swann, R

AU - Dwek, M

AU - Perkins, A

AU - Milne, RL

AU - Benitez, J

AU - Zamora, MP

AU - Perez, JIA

AU - Bojesen, SE

AU - Nielsen, SF

AU - Nordestgaard, BG

AU - Flyger, H

AU - Guenel, P

AU - Menegaux, F

AU - Cordina-Duverger, E

AU - Burwinkel, B

AU - Marme, F

AU - Schneeweiss, A

AU - Sohn, C

AU - Sawyer, E

AU - Tomlinson, I

AU - Kerin, MJ

AU - Peto, J

AU - Johnson, N

AU - Fletcher, O

AU - Silva, ID

AU - Fasching, PA

AU - Beckmann, MW

AU - Hartmann, A

AU - Ekici, AB

AU - Lophatananon, A

AU - Muir, K

AU - Puttawibul, P

AU - Wiangnon, S

AU - Schmidt, Marjanka K

AU - Broeks, A

AU - Braaf, LM

AU - Rosenberg, EH

AU - Hopper, JL

AU - Apicella, C

AU - Park, DJ

AU - Southey, MC

AU - Swerdlow, AJ

AU - Ashworth, A

AU - Orr, N

AU - Schoemaker, MJ

AU - Anton-Culver, H

AU - Ziogas, A

AU - Bernstein, L

AU - Dur, CC

AU - Shen, CY

AU - Yu, JC

AU - Hsu, HM

AU - Hsiung, CN

AU - Hamann, U

AU - Dunnebier, T

AU - Rudiger, T

AU - Ulmer, HU

AU - Pharoah, PP

AU - Dunning, AM

AU - Humphreys, MK

AU - Wang, Q (Qing)

AU - Cox, A

AU - Cross, SS

AU - Reed, MW

AU - Hall, P

AU - Czene, K

AU - Ambrosone, CB

AU - Ademuyiwa, F

AU - Hwang, H

AU - Eccles, DM

AU - Garcia-Closas, M

AU - Figueroa, JD

AU - Sherman, ME

AU - Lissowska, J

AU - Devilee, P

AU - Seynaeve, Caroline

AU - Tollenaar, RAEM

AU - Hooning, Maartje

AU - Andrulis, IL

AU - Knight, JA

AU - Glendon, G

AU - Mulligan, AM

AU - Winqvist, R

AU - Pylkas, K

AU - Jukkola-Vuorinen, A

AU - Grip, M

AU - John, EM

AU - Miron, A

AU - Alnaes, GG

AU - Kristensen, V

AU - Borresen-Dale, AL

AU - Giles, GG

AU - Baglietto, L

AU - McLean, CA

AU - Severi, G

AU - Kosel, ML

AU - Pankratz, VS

AU - Slager, S

AU - Olson, JE

AU - Radice, P

AU - Peterlongo, P

AU - Manoukian, S

AU - Barile, M

AU - Lambrechts, D

AU - Hatse, S

AU - Dieudonne, AS

AU - Christiaens, MR

AU - Chenevix-Trench, G

AU - Beesley, J

AU - Chen, XQ

AU - Mannermaa, A

AU - Kosma, VM

AU - Hartikainen, JM

AU - Soini, Y

AU - Easton, DF

AU - Couch, FJ

AU - Truong, T

PY - 2012

Y1 - 2012

N2 - The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 x 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 x 10(-7)). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18-1.33; P = 3.31 x 10-(13)]. Thus, 19p13.1 is the first triple-negativespecific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795-803. (C)2012 AACR.

AB - The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 x 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 x 10(-7)). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89-1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18-1.33; P = 3.31 x 10-(13)]. Thus, 19p13.1 is the first triple-negativespecific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795-803. (C)2012 AACR.

U2 - 10.1158/0008-5472.CAN-11-3364

DO - 10.1158/0008-5472.CAN-11-3364

M3 - Article

C2 - 22331459

SN - 0008-5472

VL - 72

SP - 1795

EP - 1803

JO - Cancer Research

JF - Cancer Research

IS - 7

ER -