Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: Findings from the Breast Cancer Association Consortium

Annegien Broeks; Marjanka K. Schmidt; Mark E Sherman; Fergus J Couch; John L. Hopper; Gillian S Dite; Carmel Apicella; Letitia D Smith; Fleur Hammet; Melissa C. Southey; Laura J. Van't Veer; Renate De Groot; Vincent T.H.B.M. Smit; Peter A. Fasching; Matthias W. Beckmann; Sebastian M Jud; Arif B Ekici; Arndt Hartmann; Alexander Hein; Ruediger Schulz-wendtland; Barbara Burwinkel; Frederik Marme; Andreas Schneeweiss; Hans Peter Sinn; Christof Sohn; Sandrine Tchatchou; Stig E Bojesen; Børge G. Nordestgaard; Henrik Flyger; David D. Ørsted; Diljit Kaur-Knudsen; Roger L Milne; Jose I.Arias Pérez; Pilar Zamora; Primitiva Menéndez Rodríguez; Javier Benítez; Hiltrud Brauch; Christina Justenhoven; Yon-Dschun Ko; The Genica Network; Ute Hamann; Hans-Peter Fischer; Thomas Brüning; Beate Pesch; Jenny Chang-Claude; Shan Wang-Gohrke; Michael Bremer; Johann H. Karstens; Peter Hillemanns; Thilo Dörk; Heli A. Nevanlinna; Tuomas Heikkinen; Päivi Heikkilä; Carl Blomqvist; Kristiina Aittomäki; Kirsimari Aaltonen; Annika Lindblom; Sara Margolin; Arto Mannermaa; Veli-Matti Kosma; Jaana M. Kauppinen; Vesa Kataja; Päivi Auvinen; Matti Eskelinen; Ylermi Soini; Georgia Chenevix-Trench; Amanda B Spurdle; Jonathan  Beesley; Xiaoqing Chen; Helene Holland; Diether Lambrechts; Bart Claes; Thijs Vandorpe; Patrick Neven; Hans Wildiers; Dieter Flesch-Janys; Rebecca Hein; Thomas Löning; Matthew Kosel; Zachary S. Fredericksen; Xianshu Wang; Graham G. Giles; Laura Baglietto; Gianluca Severi; Catriona McLean; Christopher A Haiman; Brian E Henderson; Loic Le Marchand; Laurence N Kolonel; Grethe Grenaker Alnæs; Vessela Kristensen; Anne Lise Børresen-Dale; David J. Hunter; Susan E Hankinson; Irene L Andrulis; Anna Marie Mulligan; Frances P O'Malley; Peter Devilee; Petra E.A. Huijts; Rob A.E.M. Tollenaar; Christi J. Van Asperen; Caroline S. Seynaeve; Stephen J Chanock; Jolanta Lissowska; Louise Brinton; Beata Peplonska; Jonine D Figueroa; Xiaohong R Yang; Maartje J Hooning; Antoinette Hollestelle; Rogier A. Oldenburg; Agnes Jager; Mieke Kriege; Bahar Ozturk; Geert J.L.H. Van Leenders; Per Hall; Kamila Czene; Keith Humphreys; Jianjun Liu; Angela Cox; Daniel Connley; Helen E Cramp; Simon S Cross; Sabapathy P Balasubramanian; Malcolm W R Reed; Alison M Dunning; Douglas F Easton; Manjeet K. Humphreys; Carlos Caldas; Fiona Blows; Kristy Driver; Elena Provenzano; Jan Lubinski; Anna Jakubowska; Tomasz Huzarski; Tomasz Byrski; Cezary Cybulski; Bohdan Gorski; Jacek Gronwald; Paul Brennan; Suleeporn Sangrajrang; Valerie Gaborieau; Chen-Yang Shen; Chia-Ni Hsiung; Jyh-Cherng Yu; Shou-Tung Chen; Giu-Cheng Hsu; Ming-Feng Hou; Chiun Sheng Huang; Hoda Anton-Culver; Argyrios Ziogas; Paul D P Pharoah; Montserrat Garcia-Closas; kConFab51; AOCS50,51

doi:10.1093/hmg/ddr228

Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: Findings from the Breast Cancer Association Consortium

Annegien Broeks, Marjanka K. Schmidt, Mark E Sherman, Fergus J Couch, John L. Hopper, Gillian S Dite, Carmel Apicella, Letitia D Smith, Fleur Hammet, Melissa C. Southey, Laura J. Van't Veer, Renate De Groot, Vincent T.H.B.M. Smit, Peter A. Fasching, Matthias W. Beckmann, Sebastian M Jud, Arif B Ekici, Arndt Hartmann, Alexander Hein, Ruediger Schulz-wendtlandBarbara Burwinkel, Frederik Marme, Andreas Schneeweiss, Hans Peter Sinn, Christof Sohn, Sandrine Tchatchou, Stig E Bojesen, Børge G. Nordestgaard, Henrik Flyger, David D. Ørsted, Diljit Kaur-Knudsen, Roger L Milne, Jose I.Arias Pérez, Pilar Zamora, Primitiva Menéndez Rodríguez, Javier Benítez, Hiltrud Brauch, Christina Justenhoven, Yon-Dschun Ko, The Genica Network, Ute Hamann, Hans-Peter Fischer, Thomas Brüning, Beate Pesch, Jenny Chang-Claude, Shan Wang-Gohrke, Michael Bremer, Johann H. Karstens, Peter Hillemanns, Thilo Dörk, Heli A. Nevanlinna, Tuomas Heikkinen, Päivi Heikkilä, Carl Blomqvist, Kristiina Aittomäki, Kirsimari Aaltonen, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Jaana M. Kauppinen, Vesa Kataja, Päivi Auvinen, Matti Eskelinen, Ylermi Soini, Georgia Chenevix-Trench, Amanda B Spurdle, Jonathan Beesley, Xiaoqing Chen, Helene Holland, Diether Lambrechts, Bart Claes, Thijs Vandorpe, Patrick Neven, Hans Wildiers, Dieter Flesch-Janys, Rebecca Hein, Thomas Löning, Matthew Kosel, Zachary S. Fredericksen, Xianshu Wang, Graham G. Giles, Laura Baglietto, Gianluca Severi, Catriona McLean, Christopher A Haiman, Brian E Henderson, Loic Le Marchand, Laurence N Kolonel, Grethe Grenaker Alnæs, Vessela Kristensen, Anne Lise Børresen-Dale, David J. Hunter, Susan E Hankinson, Irene L Andrulis, Anna Marie Mulligan, Frances P O'Malley, Peter Devilee, Petra E.A. Huijts, Rob A.E.M. Tollenaar, Christi J. Van Asperen, Caroline S. Seynaeve, Stephen J Chanock, Jolanta Lissowska, Louise Brinton, Beata Peplonska, Jonine D Figueroa, Xiaohong R Yang, Maartje J Hooning, Antoinette Hollestelle, Rogier A. Oldenburg, Agnes Jager, Mieke Kriege, Bahar Ozturk, Geert J.L.H. Van Leenders, Per Hall, Kamila Czene, Keith Humphreys, Jianjun Liu, Angela Cox, Daniel Connley, Helen E Cramp, Simon S Cross, Sabapathy P Balasubramanian, Malcolm W R Reed, Alison M Dunning, Douglas F Easton, Manjeet K. Humphreys, Carlos Caldas, Fiona Blows, Kristy Driver, Elena Provenzano, Jan Lubinski, Anna Jakubowska, Tomasz Huzarski, Tomasz Byrski, Cezary Cybulski, Bohdan Gorski, Jacek Gronwald, Paul Brennan, Suleeporn Sangrajrang, Valerie Gaborieau, Chen-Yang Shen, Chia-Ni Hsiung, Jyh-Cherng Yu, Shou-Tung Chen, Giu-Cheng Hsu, Ming-Feng Hou, Chiun Sheng Huang, Hoda Anton-Culver, Argyrios Ziogas, Paul D P Pharoah, Montserrat Garcia-Closas, kConFab51, AOCS50,51

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

148 Citations (Scopus)

Abstract

Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER1 than ER2 tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10^-18), rs3803662 (16q12) (P = 3.7 × 10^-5), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10^-6 and P = 4.1 × 10^-4, respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.

Original language	English
Pages (from-to)	3289-3303
Number of pages	15
Journal	Human Molecular Genetics
Volume	20
Issue number	16
DOIs	https://doi.org/10.1093/hmg/ddr228
Publication status	Published - 2011
Externally published	Yes

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10.1093/hmg/ddr228

Cite this

Broeks, A., Schmidt, M. K., Sherman, M. E., Couch, F. J., Hopper, J. L., Dite, G. S., Apicella, C., Smith, L. D., Hammet, F., Southey, M. C., Van't Veer, L. J., De Groot, R., Smit, V. T. H. B. M., Fasching, P. A., Beckmann, M. W., Jud, S. M., Ekici, A. B., Hartmann, A., Hein, A., ... AOCS50,51 (2011). Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: Findings from the Breast Cancer Association Consortium. Human Molecular Genetics, 20(16), 3289-3303. https://doi.org/10.1093/hmg/ddr228

@article{fa72d1ea2aa9471bbac38ecae6a57c29,

title = "Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: Findings from the Breast Cancer Association Consortium",

abstract = "Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER1 than ER2 tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10-18), rs3803662 (16q12) (P = 3.7 × 10-5), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10-6 and P = 4.1 × 10-4, respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.",

author = "Annegien Broeks and Schmidt, {Marjanka K.} and Sherman, {Mark E} and Couch, {Fergus J} and Hopper, {John L.} and Dite, {Gillian S} and Carmel Apicella and Smith, {Letitia D} and Fleur Hammet and Southey, {Melissa C.} and {Van't Veer}, {Laura J.} and {De Groot}, Renate and Smit, {Vincent T.H.B.M.} and Fasching, {Peter A.} and Beckmann, {Matthias W.} and Jud, {Sebastian M} and Ekici, {Arif B} and Arndt Hartmann and Alexander Hein and Ruediger Schulz-wendtland and Barbara Burwinkel and Frederik Marme and Andreas Schneeweiss and Sinn, {Hans Peter} and Christof Sohn and Sandrine Tchatchou and Bojesen, {Stig E} and Nordestgaard, {B{\o}rge G.} and Henrik Flyger and {\O}rsted, {David D.} and Diljit Kaur-Knudsen and Milne, {Roger L} and P{\'e}rez, {Jose I.Arias} and Pilar Zamora and Rodr{\'i}guez, {Primitiva Men{\'e}ndez} and Javier Ben{\'i}tez and Hiltrud Brauch and Christina Justenhoven and Yon-Dschun Ko and Network, {The Genica} and Ute Hamann and Hans-Peter Fischer and Thomas Br{\"u}ning and Beate Pesch and Jenny Chang-Claude and Shan Wang-Gohrke and Michael Bremer and Karstens, {Johann H.} and Peter Hillemanns and Thilo D{\"o}rk and Nevanlinna, {Heli A.} and Tuomas Heikkinen and P{\"a}ivi Heikkil{\"a} and Carl Blomqvist and Kristiina Aittom{\"a}ki and Kirsimari Aaltonen and Annika Lindblom and Sara Margolin and Arto Mannermaa and Veli-Matti Kosma and Kauppinen, {Jaana M.} and Vesa Kataja and P{\"a}ivi Auvinen and Matti Eskelinen and Ylermi Soini and Georgia Chenevix-Trench and Spurdle, {Amanda B} and Jonathan Beesley and Xiaoqing Chen and Helene Holland and Diether Lambrechts and Bart Claes and Thijs Vandorpe and Patrick Neven and Hans Wildiers and Dieter Flesch-Janys and Rebecca Hein and Thomas L{\"o}ning and Matthew Kosel and Fredericksen, {Zachary S.} and Xianshu Wang and Giles, {Graham G.} and Laura Baglietto and Gianluca Severi and Catriona McLean and Haiman, {Christopher A} and Henderson, {Brian E} and {Le Marchand}, Loic and Kolonel, {Laurence N} and Aln{\ae}s, {Grethe Grenaker} and Vessela Kristensen and B{\o}rresen-Dale, {Anne Lise} and Hunter, {David J.} and Hankinson, {Susan E} and Andrulis, {Irene L} and Mulligan, {Anna Marie} and O'Malley, {Frances P} and Peter Devilee and Huijts, {Petra E.A.} and Tollenaar, {Rob A.E.M.} and {Van Asperen}, {Christi J.} and Seynaeve, {Caroline S.} and Chanock, {Stephen J} and Jolanta Lissowska and Louise Brinton and Beata Peplonska and Figueroa, {Jonine D} and Yang, {Xiaohong R} and Hooning, {Maartje J} and Antoinette Hollestelle and Oldenburg, {Rogier A.} and Agnes Jager and Mieke Kriege and Bahar Ozturk and {Van Leenders}, {Geert J.L.H.} and Per Hall and Kamila Czene and Keith Humphreys and Jianjun Liu and Angela Cox and Daniel Connley and Cramp, {Helen E} and Cross, {Simon S} and Balasubramanian, {Sabapathy P} and Reed, {Malcolm W R} and Dunning, {Alison M} and Easton, {Douglas F} and Humphreys, {Manjeet K.} and Carlos Caldas and Fiona Blows and Kristy Driver and Elena Provenzano and Jan Lubinski and Anna Jakubowska and Tomasz Huzarski and Tomasz Byrski and Cezary Cybulski and Bohdan Gorski and Jacek Gronwald and Paul Brennan and Suleeporn Sangrajrang and Valerie Gaborieau and Chen-Yang Shen and Chia-Ni Hsiung and Jyh-Cherng Yu and Shou-Tung Chen and Giu-Cheng Hsu and Ming-Feng Hou and Huang, {Chiun Sheng} and Hoda Anton-Culver and Argyrios Ziogas and Pharoah, {Paul D P} and Montserrat Garcia-Closas and kConFab51 and AOCS50,51",

year = "2011",

doi = "10.1093/hmg/ddr228",

language = "English",

volume = "20",

pages = "3289--3303",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "16",

}

Broeks, A, Schmidt, MK, Sherman, ME, Couch, FJ, Hopper, JL, Dite, GS, Apicella, C, Smith, LD, Hammet, F, Southey, MC, Van't Veer, LJ, De Groot, R, Smit, VTHBM, Fasching, PA, Beckmann, MW, Jud, SM, Ekici, AB, Hartmann, A, Hein, A, Schulz-wendtland, R, Burwinkel, B, Marme, F, Schneeweiss, A, Sinn, HP, Sohn, C, Tchatchou, S, Bojesen, SE, Nordestgaard, BG, Flyger, H, Ørsted, DD, Kaur-Knudsen, D, Milne, RL, Pérez, JIA, Zamora, P, Rodríguez, PM, Benítez, J, Brauch, H, Justenhoven, C, Ko, Y-D, Network, TG, Hamann, U, Fischer, H-P, Brüning, T, Pesch, B, Chang-Claude, J, Wang-Gohrke, S, Bremer, M, Karstens, JH, Hillemanns, P, Dörk, T, Nevanlinna, HA, Heikkinen, T, Heikkilä, P, Blomqvist, C, Aittomäki, K, Aaltonen, K, Lindblom, A, Margolin, S, Mannermaa, A, Kosma, V-M, Kauppinen, JM, Kataja, V, Auvinen, P, Eskelinen, M, Soini, Y, Chenevix-Trench, G, Spurdle, AB, Beesley, J, Chen, X, Holland, H, Lambrechts, D, Claes, B, Vandorpe, T, Neven, P, Wildiers, H, Flesch-Janys, D, Hein, R, Löning, T, Kosel, M, Fredericksen, ZS, Wang, X, Giles, GG, Baglietto, L, Severi, G, McLean, C, Haiman, CA, Henderson, BE, Le Marchand, L, Kolonel, LN, Alnæs, GG, Kristensen, V, Børresen-Dale, AL, Hunter, DJ, Hankinson, SE, Andrulis, IL, Mulligan, AM, O'Malley, FP, Devilee, P, Huijts, PEA, Tollenaar, RAEM, Van Asperen, CJ, Seynaeve, CS, Chanock, SJ, Lissowska, J, Brinton, L, Peplonska, B, Figueroa, JD, Yang, XR, Hooning, MJ, Hollestelle, A, Oldenburg, RA, Jager, A, Kriege, M, Ozturk, B, Van Leenders, GJLH, Hall, P, Czene, K, Humphreys, K, Liu, J, Cox, A, Connley, D, Cramp, HE, Cross, SS, Balasubramanian, SP, Reed, MWR, Dunning, AM, Easton, DF, Humphreys, MK, Caldas, C, Blows, F, Driver, K, Provenzano, E, Lubinski, J, Jakubowska, A, Huzarski, T, Byrski, T, Cybulski, C, Gorski, B, Gronwald, J, Brennan, P, Sangrajrang, S, Gaborieau, V, Shen, C-Y, Hsiung, C-N, Yu, J-C, Chen, S-T, Hsu, G-C, Hou, M-F, Huang, CS, Anton-Culver, H, Ziogas, A, Pharoah, PDP, Garcia-Closas, M, kConFab51 & AOCS50,51 2011, 'Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: Findings from the Breast Cancer Association Consortium', Human Molecular Genetics, vol. 20, no. 16, pp. 3289-3303. https://doi.org/10.1093/hmg/ddr228

TY - JOUR

T1 - Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

T2 - Findings from the Breast Cancer Association Consortium

AU - Broeks, Annegien

AU - Schmidt, Marjanka K.

AU - Sherman, Mark E

AU - Couch, Fergus J

AU - Hopper, John L.

AU - Dite, Gillian S

AU - Apicella, Carmel

AU - Smith, Letitia D

AU - Hammet, Fleur

AU - Southey, Melissa C.

AU - Van't Veer, Laura J.

AU - De Groot, Renate

AU - Smit, Vincent T.H.B.M.

AU - Fasching, Peter A.

AU - Beckmann, Matthias W.

AU - Jud, Sebastian M

AU - Ekici, Arif B

AU - Hartmann, Arndt

AU - Hein, Alexander

AU - Schulz-wendtland, Ruediger

AU - Burwinkel, Barbara

AU - Marme, Frederik

AU - Schneeweiss, Andreas

AU - Sinn, Hans Peter

AU - Sohn, Christof

AU - Tchatchou, Sandrine

AU - Bojesen, Stig E

AU - Nordestgaard, Børge G.

AU - Flyger, Henrik

AU - Ørsted, David D.

AU - Kaur-Knudsen, Diljit

AU - Milne, Roger L

AU - Pérez, Jose I.Arias

AU - Zamora, Pilar

AU - Rodríguez, Primitiva Menéndez

AU - Benítez, Javier

AU - Brauch, Hiltrud

AU - Justenhoven, Christina

AU - Ko, Yon-Dschun

AU - Network, The Genica

AU - Hamann, Ute

AU - Fischer, Hans-Peter

AU - Brüning, Thomas

AU - Pesch, Beate

AU - Chang-Claude, Jenny

AU - Wang-Gohrke, Shan

AU - Bremer, Michael

AU - Karstens, Johann H.

AU - Hillemanns, Peter

AU - Dörk, Thilo

AU - Nevanlinna, Heli A.

AU - Heikkinen, Tuomas

AU - Heikkilä, Päivi

AU - Blomqvist, Carl

AU - Aittomäki, Kristiina

AU - Aaltonen, Kirsimari

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Mannermaa, Arto

AU - Kosma, Veli-Matti

AU - Kauppinen, Jaana M.

AU - Kataja, Vesa

AU - Auvinen, Päivi

AU - Eskelinen, Matti

AU - Soini, Ylermi

AU - Chenevix-Trench, Georgia

AU - Spurdle, Amanda B

AU - Beesley, Jonathan

AU - Chen, Xiaoqing

AU - Holland, Helene

AU - Lambrechts, Diether

AU - Claes, Bart

AU - Vandorpe, Thijs

AU - Neven, Patrick

AU - Wildiers, Hans

AU - Flesch-Janys, Dieter

AU - Hein, Rebecca

AU - Löning, Thomas

AU - Kosel, Matthew

AU - Fredericksen, Zachary S.

AU - Wang, Xianshu

AU - Giles, Graham G.

AU - Baglietto, Laura

AU - Severi, Gianluca

AU - McLean, Catriona

AU - Haiman, Christopher A

AU - Henderson, Brian E

AU - Le Marchand, Loic

AU - Kolonel, Laurence N

AU - Alnæs, Grethe Grenaker

AU - Kristensen, Vessela

AU - Børresen-Dale, Anne Lise

AU - Hunter, David J.

AU - Hankinson, Susan E

AU - Andrulis, Irene L

AU - Mulligan, Anna Marie

AU - O'Malley, Frances P

AU - Devilee, Peter

AU - Huijts, Petra E.A.

AU - Tollenaar, Rob A.E.M.

AU - Van Asperen, Christi J.

AU - Seynaeve, Caroline S.

AU - Chanock, Stephen J

AU - Lissowska, Jolanta

AU - Brinton, Louise

AU - Peplonska, Beata

AU - Figueroa, Jonine D

AU - Yang, Xiaohong R

AU - Hooning, Maartje J

AU - Hollestelle, Antoinette

AU - Oldenburg, Rogier A.

AU - Jager, Agnes

AU - Kriege, Mieke

AU - Ozturk, Bahar

AU - Van Leenders, Geert J.L.H.

AU - Hall, Per

AU - Czene, Kamila

AU - Humphreys, Keith

AU - Liu, Jianjun

AU - Cox, Angela

AU - Connley, Daniel

AU - Cramp, Helen E

AU - Cross, Simon S

AU - Balasubramanian, Sabapathy P

AU - Reed, Malcolm W R

AU - Dunning, Alison M

AU - Easton, Douglas F

AU - Humphreys, Manjeet K.

AU - Caldas, Carlos

AU - Blows, Fiona

AU - Driver, Kristy

AU - Provenzano, Elena

AU - Lubinski, Jan

AU - Jakubowska, Anna

AU - Huzarski, Tomasz

AU - Byrski, Tomasz

AU - Cybulski, Cezary

AU - Gorski, Bohdan

AU - Gronwald, Jacek

AU - Brennan, Paul

AU - Sangrajrang, Suleeporn

AU - Gaborieau, Valerie

AU - Shen, Chen-Yang

AU - Hsiung, Chia-Ni

AU - Yu, Jyh-Cherng

AU - Chen, Shou-Tung

AU - Hsu, Giu-Cheng

AU - Hou, Ming-Feng

AU - Huang, Chiun Sheng

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Pharoah, Paul D P

AU - Garcia-Closas, Montserrat

AU - kConFab51

AU - AOCS50,51

PY - 2011

Y1 - 2011

N2 - Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER1 than ER2 tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10-18), rs3803662 (16q12) (P = 3.7 × 10-5), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10-6 and P = 4.1 × 10-4, respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.

AB - Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER1 than ER2 tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10-18), rs3803662 (16q12) (P = 3.7 × 10-5), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10-6 and P = 4.1 × 10-4, respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.

UR - http://www.scopus.com/inward/record.url?scp=80053366674&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddr228

DO - 10.1093/hmg/ddr228

M3 - Article

C2 - 21596841

AN - SCOPUS:80053366674

SN - 0964-6906

VL - 20

SP - 3289

EP - 3303

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 16

ER -

Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: Findings from the Breast Cancer Association Consortium

Abstract

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