Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)

Rebecca Hein; Melanie Maranian; John L. Hopper; Miroslaw K. Kapuscinski; Melissa C. Southey; Daniel J. Park; Marjanka K. Schmidt; Annegien Broeks; Frans B.L. Hogervorst; H. Bas Bueno-de-Mesquit; Kenneth R. Muir; Artitaya Lophatananon; Suthee Rattanamongkongul; Puttisak Puttawibul; Peter A. Fasching; Alexander Hein; Arif B. Ekici; Matthias W. Beckmann; Olivia Fletcher; Nichola Johnson; Isabel dos Santos Silva; Julian Peto; Elinor Sawyer; Ian Tomlinson; Michael Kerin; Nicola Miller; Frederick Marmee; Andreas Schneeweiss; Christof Sohn; Barbara Burwinkel; Pascal Guénel; Emilie Cordina-Duverger; Florence Menegaux; Thérèse Truong; Stig E. Bojesen; Børge G. Nordestgaard; Henrik Flyger; Roger L. Milne; Jose Ignacio Arias Perez; M. Pilar Zamora; Javier Benítez; Hoda Anton-Culver; Argyrios Ziogas; Leslie Bernstein; Christina A. Clarke; Hermann Brenner; Heiko Müller; Volker Arndt; Christa Stegmaier; Nazneen Rahman; Sheila Seal; Clare Turnbull; Anthony Renwick; Alfons Meindl; Sarah Schott; Claus R. Bartram; Rita K. Schmutzler; Hiltrud Brauch; Ute Hamann; Yon Dschun Ko; Shan Wang-Gohrke; Thilo Dörk; Peter Schürmann; Johann H. Karstens; Peter Hillemanns; Heli Nevanlinna; Tuomas Heikkinen; Kristiina Aittomäki; Carl Blomqvist; Natalia V. Bogdanova; Iosif V. Zalutsky; Natalia N. Antonenkova; Marina Bermisheva; Darya Prokovieva; Albina Farahtdinova; Elza Khusnutdinova; Annika Lindblom; Sara Margolin; Arto Mannermaa; Vesa Kataja; Veli Matti Kosma; Jaana Hartikainen; Xiaoqing Chen; Jonathan Beesley; Diether Lambrechts; Hui Zhao; Patrick Neven; Hans Wildiers; Stefan Nickels; Dieter Flesch-Janys; Paolo Radice; Paolo Peterlongo; Siranoush Manoukian; Monica Barile; Fergus J. Couch; Janet E. Olson; Xianshu Wang; Zachary Fredericksen; Graham G. Giles; Laura Baglietto; Catriona A. McLean; Gianluca Severi; Kenneth Offit; Mark Robson; Mia M. Gaudet; Joseph Vijai; Grethe Grenaker Alnæs; Vessela Kristensen; Anne Lise Børresen-Dale; Esther M. John; Alexander Miron; Robert Winqvist; Katri Pylkäs; Arja Jukkola-Vuorinen; Mervi Grip; Irene L. Andrulis; Julia A. Knight; Gord Glendon; Anna Marie Mulligan; Jonine D. Figueroa; Montserrat García-Closas; Jolanta Lissowska; Mark E. Sherman; Maartje Hooning; John W.M. Martens; Caroline Seynaeve; Margriet Collée; Per Hall; Keith Humpreys; Kamila Czene; Jianjun Liu; Angela Cox; Ian W. Brock; Simon S. Cross; Malcolm W.R. Reed; Shahana Ahmed; Maya Ghoussaini; Paul DP Pharoah; Daehee Kang; Keun Young Yoo; Dong Young Noh; Anna Jakubowska; Katarzyna Jaworska; Katarzyna Durda; Elzbieta Złowocka; Suleeporn Sangrajrang; Valerie Gaborieau; Paul Brennan; James McKay; Chen Yang Shen; Jyh Cherng Yu; Huan Ming Hsu; Ming Feng Hou; Nick Orr; Minouk Schoemaker; Alan Ashworth; Anthony Swerdlow; Amy Trentham-Dietz; Polly A. Newcomb; Linda Titus; Kathleen M. Egan; Georgia Chenevix-Trench; Antonis C. Antoniou; Manjeet K. Humphreys; Jonathan Morrison; Jenny Chang-Claude; Douglas F. Easton; Alison M. Dunning

doi:10.1371/journal.pone.0042380

Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)

Rebecca Hein, Melanie Maranian, John L. Hopper, Miroslaw K. Kapuscinski, Melissa C. Southey, Daniel J. Park, Marjanka K. Schmidt, Annegien Broeks, Frans B.L. Hogervorst, H. Bas Bueno-de-Mesquit, Kenneth R. Muir, Artitaya Lophatananon, Suthee Rattanamongkongul, Puttisak Puttawibul, Peter A. Fasching, Alexander Hein, Arif B. Ekici, Matthias W. Beckmann, Olivia Fletcher, Nichola JohnsonIsabel dos Santos Silva, Julian Peto, Elinor Sawyer, Ian Tomlinson, Michael Kerin, Nicola Miller, Frederick Marmee, Andreas Schneeweiss, Christof Sohn, Barbara Burwinkel, Pascal Guénel, Emilie Cordina-Duverger, Florence Menegaux, Thérèse Truong, Stig E. Bojesen, Børge G. Nordestgaard, Henrik Flyger, Roger L. Milne, Jose Ignacio Arias Perez, M. Pilar Zamora, Javier Benítez, Hoda Anton-Culver, Argyrios Ziogas, Leslie Bernstein, Christina A. Clarke, Hermann Brenner, Heiko Müller, Volker Arndt, Christa Stegmaier, Nazneen Rahman, Sheila Seal, Clare Turnbull, Anthony Renwick, Alfons Meindl, Sarah Schott, Claus R. Bartram, Rita K. Schmutzler, Hiltrud Brauch, Ute Hamann, Yon Dschun Ko, Shan Wang-Gohrke, Thilo Dörk, Peter Schürmann, Johann H. Karstens, Peter Hillemanns, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Natalia V. Bogdanova, Iosif V. Zalutsky, Natalia N. Antonenkova, Marina Bermisheva, Darya Prokovieva, Albina Farahtdinova, Elza Khusnutdinova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli Matti Kosma, Jaana Hartikainen, Xiaoqing Chen, Jonathan Beesley, Diether Lambrechts, Hui Zhao, Patrick Neven, Hans Wildiers, Stefan Nickels, Dieter Flesch-Janys, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Fergus J. Couch, Janet E. Olson, Xianshu Wang, Zachary Fredericksen, Graham G. Giles, Laura Baglietto, Catriona A. McLean, Gianluca Severi, Kenneth Offit, Mark Robson, Mia M. Gaudet, Joseph Vijai, Grethe Grenaker Alnæs, Vessela Kristensen, Anne Lise Børresen-Dale, Esther M. John, Alexander Miron, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Anna Marie Mulligan, Jonine D. Figueroa, Montserrat García-Closas, Jolanta Lissowska, Mark E. Sherman, Maartje Hooning, John W.M. Martens, Caroline Seynaeve, Margriet Collée, Per Hall, Keith Humpreys, Kamila Czene, Jianjun Liu, Angela Cox, Ian W. Brock, Simon S. Cross, Malcolm W.R. Reed, Shahana Ahmed, Maya Ghoussaini, Paul DP Pharoah, Daehee Kang, Keun Young Yoo, Dong Young Noh, Anna Jakubowska, Katarzyna Jaworska, Katarzyna Durda, Elzbieta Złowocka, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Chen Yang Shen, Jyh Cherng Yu, Huan Ming Hsu, Ming Feng Hou, Nick Orr, Minouk Schoemaker, Alan Ashworth, Anthony Swerdlow, Amy Trentham-Dietz, Polly A. Newcomb, Linda Titus, Kathleen M. Egan, Georgia Chenevix-Trench, Antonis C. Antoniou, Manjeet K. Humphreys, Jonathan Morrison, Jenny Chang-Claude, Douglas F. Easton, Alison M. Dunning

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

51 Citations (Scopus)

Abstract

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6×10^-14 in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8×10^-18 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2×10^-9 in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8×10^-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8×10^-17 versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3×10^-7, p_{heterogeneity} = 5.1×10^-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.

Original language	English
Article number	e42380
Journal	PLoS ONE
Volume	7
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0042380
Publication status	Published - 7 Aug 2012
Externally published	Yes

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10.1371/journal.pone.0042380

Cite this

Hein, R., Maranian, M., Hopper, J. L., Kapuscinski, M. K., Southey, M. C., Park, D. J., Schmidt, M. K., Broeks, A., Hogervorst, F. B. L., Bueno-de-Mesquit, H. B., Muir, K. R., Lophatananon, A., Rattanamongkongul, S., Puttawibul, P., Fasching, P. A., Hein, A., Ekici, A. B., Beckmann, M. W., Fletcher, O., ... Dunning, A. M. (2012). Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC). PLoS ONE, 7(8), Article e42380. https://doi.org/10.1371/journal.pone.0042380

@article{79d05e8956ad400e8768abf4c378ad65,

title = "Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)",

abstract = "The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6×10-14 in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8×10-18 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2×10-9 in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8×10-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8×10-17 versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3×10-7, pheterogeneity = 5.1×10-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.",

author = "Rebecca Hein and Melanie Maranian and Hopper, {John L.} and Kapuscinski, {Miroslaw K.} and Southey, {Melissa C.} and Park, {Daniel J.} and Schmidt, {Marjanka K.} and Annegien Broeks and Hogervorst, {Frans B.L.} and Bueno-de-Mesquit, {H. Bas} and Muir, {Kenneth R.} and Artitaya Lophatananon and Suthee Rattanamongkongul and Puttisak Puttawibul and Fasching, {Peter A.} and Alexander Hein and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Olivia Fletcher and Nichola Johnson and {dos Santos Silva}, Isabel and Julian Peto and Elinor Sawyer and Ian Tomlinson and Michael Kerin and Nicola Miller and Frederick Marmee and Andreas Schneeweiss and Christof Sohn and Barbara Burwinkel and Pascal Gu{\'e}nel and Emilie Cordina-Duverger and Florence Menegaux and Th{\'e}r{\`e}se Truong and Bojesen, {Stig E.} and Nordestgaard, {B{\o}rge G.} and Henrik Flyger and Milne, {Roger L.} and Perez, {Jose Ignacio Arias} and Zamora, {M. Pilar} and Javier Ben{\'i}tez and Hoda Anton-Culver and Argyrios Ziogas and Leslie Bernstein and Clarke, {Christina A.} and Hermann Brenner and Heiko M{\"u}ller and Volker Arndt and Christa Stegmaier and Nazneen Rahman and Sheila Seal and Clare Turnbull and Anthony Renwick and Alfons Meindl and Sarah Schott and Bartram, {Claus R.} and Schmutzler, {Rita K.} and Hiltrud Brauch and Ute Hamann and Ko, {Yon Dschun} and Shan Wang-Gohrke and Thilo D{\"o}rk and Peter Sch{\"u}rmann and Karstens, {Johann H.} and Peter Hillemanns and Heli Nevanlinna and Tuomas Heikkinen and Kristiina Aittom{\"a}ki and Carl Blomqvist and Bogdanova, {Natalia V.} and Zalutsky, {Iosif V.} and Antonenkova, {Natalia N.} and Marina Bermisheva and Darya Prokovieva and Albina Farahtdinova and Elza Khusnutdinova and Annika Lindblom and Sara Margolin and Arto Mannermaa and Vesa Kataja and Kosma, {Veli Matti} and Jaana Hartikainen and Xiaoqing Chen and Jonathan Beesley and Diether Lambrechts and Hui Zhao and Patrick Neven and Hans Wildiers and Stefan Nickels and Dieter Flesch-Janys and Paolo Radice and Paolo Peterlongo and Siranoush Manoukian and Monica Barile and Couch, {Fergus J.} and Olson, {Janet E.} and Xianshu Wang and Zachary Fredericksen and Giles, {Graham G.} and Laura Baglietto and McLean, {Catriona A.} and Gianluca Severi and Kenneth Offit and Mark Robson and Gaudet, {Mia M.} and Joseph Vijai and Aln{\ae}s, {Grethe Grenaker} and Vessela Kristensen and B{\o}rresen-Dale, {Anne Lise} and John, {Esther M.} and Alexander Miron and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Andrulis, {Irene L.} and Knight, {Julia A.} and Gord Glendon and Mulligan, {Anna Marie} and Figueroa, {Jonine D.} and Montserrat Garc{\'i}a-Closas and Jolanta Lissowska and Sherman, {Mark E.} and Maartje Hooning and Martens, {John W.M.} and Caroline Seynaeve and Margriet Coll{\'e}e and Per Hall and Keith Humpreys and Kamila Czene and Jianjun Liu and Angela Cox and Brock, {Ian W.} and Cross, {Simon S.} and Reed, {Malcolm W.R.} and Shahana Ahmed and Maya Ghoussaini and Pharoah, {Paul DP} and Daehee Kang and Yoo, {Keun Young} and Noh, {Dong Young} and Anna Jakubowska and Katarzyna Jaworska and Katarzyna Durda and Elzbieta Z{\l}owocka and Suleeporn Sangrajrang and Valerie Gaborieau and Paul Brennan and James McKay and Shen, {Chen Yang} and Yu, {Jyh Cherng} and Hsu, {Huan Ming} and Hou, {Ming Feng} and Nick Orr and Minouk Schoemaker and Alan Ashworth and Anthony Swerdlow and Amy Trentham-Dietz and Newcomb, {Polly A.} and Linda Titus and Egan, {Kathleen M.} and Georgia Chenevix-Trench and Antoniou, {Antonis C.} and Humphreys, {Manjeet K.} and Jonathan Morrison and Jenny Chang-Claude and Easton, {Douglas F.} and Dunning, {Alison M.}",

year = "2012",

month = aug,

day = "7",

doi = "10.1371/journal.pone.0042380",

language = "English",

volume = "7",

journal = "PLoS ONE",

issn = "1932-6203",

number = "8",

}

Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, MK, Broeks, A, Hogervorst, FBL, Bueno-de-Mesquit, HB, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, dos Santos Silva, I, Peto, J, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Marmee, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guénel, P, Cordina-Duverger, E, Menegaux, F, Truong, T, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, RL, Perez, JIA, Zamora, MP, Benítez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Müller, H, Arndt, V, Stegmaier, C, Rahman, N, Seal, S, Turnbull, C, Renwick, A, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Brauch, H, Hamann, U, Ko, YD, Wang-Gohrke, S, Dörk, T, Schürmann, P, Karstens, JH, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomäki, K, Blomqvist, C, Bogdanova, NV, Zalutsky, IV, Antonenkova, NN, Bermisheva, M, Prokovieva, D, Farahtdinova, A, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, J, Chen, X, Beesley, J, Lambrechts, D, Zhao, H, Neven, P, Wildiers, H, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Couch, FJ, Olson, JE, Wang, X, Fredericksen, Z, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Offit, K, Robson, M, Gaudet, MM, Vijai, J, Alnæs, GG, Kristensen, V, Børresen-Dale, AL, John, EM, Miron, A, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Figueroa, JD, García-Closas, M, Lissowska, J, Sherman, ME, Hooning, M, Martens, JWM, Seynaeve, C, Collée, M, Hall, P, Humpreys, K, Czene, K, Liu, J, Cox, A, Brock, IW, Cross, SS, Reed, MWR, Ahmed, S, Ghoussaini, M, Pharoah, PDP, Kang, D, Yoo, KY, Noh, DY, Jakubowska, A, Jaworska, K, Durda, K, Złowocka, E, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Shen, CY, Yu, JC, Hsu, HM, Hou, MF, Orr, N, Schoemaker, M, Ashworth, A, Swerdlow, A, Trentham-Dietz, A, Newcomb, PA, Titus, L, Egan, KM, Chenevix-Trench, G, Antoniou, AC, Humphreys, MK, Morrison, J, Chang-Claude, J, Easton, DF & Dunning, AM 2012, 'Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)', PLoS ONE, vol. 7, no. 8, e42380. https://doi.org/10.1371/journal.pone.0042380

TY - JOUR

T1 - Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)

AU - Hein, Rebecca

AU - Maranian, Melanie

AU - Hopper, John L.

AU - Kapuscinski, Miroslaw K.

AU - Southey, Melissa C.

AU - Park, Daniel J.

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Hogervorst, Frans B.L.

AU - Bueno-de-Mesquit, H. Bas

AU - Muir, Kenneth R.

AU - Lophatananon, Artitaya

AU - Rattanamongkongul, Suthee

AU - Puttawibul, Puttisak

AU - Fasching, Peter A.

AU - Hein, Alexander

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Fletcher, Olivia

AU - Johnson, Nichola

AU - dos Santos Silva, Isabel

AU - Peto, Julian

AU - Sawyer, Elinor

AU - Tomlinson, Ian

AU - Kerin, Michael

AU - Miller, Nicola

AU - Marmee, Frederick

AU - Schneeweiss, Andreas

AU - Sohn, Christof

AU - Burwinkel, Barbara

AU - Guénel, Pascal

AU - Cordina-Duverger, Emilie

AU - Menegaux, Florence

AU - Truong, Thérèse

AU - Bojesen, Stig E.

AU - Nordestgaard, Børge G.

AU - Flyger, Henrik

AU - Milne, Roger L.

AU - Perez, Jose Ignacio Arias

AU - Zamora, M. Pilar

AU - Benítez, Javier

AU - Anton-Culver, Hoda

AU - Ziogas, Argyrios

AU - Bernstein, Leslie

AU - Clarke, Christina A.

AU - Brenner, Hermann

AU - Müller, Heiko

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Rahman, Nazneen

AU - Seal, Sheila

AU - Turnbull, Clare

AU - Renwick, Anthony

AU - Meindl, Alfons

AU - Schott, Sarah

AU - Bartram, Claus R.

AU - Schmutzler, Rita K.

AU - Brauch, Hiltrud

AU - Hamann, Ute

AU - Ko, Yon Dschun

AU - Wang-Gohrke, Shan

AU - Dörk, Thilo

AU - Schürmann, Peter

AU - Karstens, Johann H.

AU - Hillemanns, Peter

AU - Nevanlinna, Heli

AU - Heikkinen, Tuomas

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V.

AU - Zalutsky, Iosif V.

AU - Antonenkova, Natalia N.

AU - Bermisheva, Marina

AU - Prokovieva, Darya

AU - Farahtdinova, Albina

AU - Khusnutdinova, Elza

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli Matti

AU - Hartikainen, Jaana

AU - Chen, Xiaoqing

AU - Beesley, Jonathan

AU - Lambrechts, Diether

AU - Zhao, Hui

AU - Neven, Patrick

AU - Wildiers, Hans

AU - Nickels, Stefan

AU - Flesch-Janys, Dieter

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Manoukian, Siranoush

AU - Barile, Monica

AU - Couch, Fergus J.

AU - Olson, Janet E.

AU - Wang, Xianshu

AU - Fredericksen, Zachary

AU - Giles, Graham G.

AU - Baglietto, Laura

AU - McLean, Catriona A.

AU - Severi, Gianluca

AU - Offit, Kenneth

AU - Robson, Mark

AU - Gaudet, Mia M.

AU - Vijai, Joseph

AU - Alnæs, Grethe Grenaker

AU - Kristensen, Vessela

AU - Børresen-Dale, Anne Lise

AU - John, Esther M.

AU - Miron, Alexander

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Glendon, Gord

AU - Mulligan, Anna Marie

AU - Figueroa, Jonine D.

AU - García-Closas, Montserrat

AU - Lissowska, Jolanta

AU - Sherman, Mark E.

AU - Hooning, Maartje

AU - Martens, John W.M.

AU - Seynaeve, Caroline

AU - Collée, Margriet

AU - Hall, Per

AU - Humpreys, Keith

AU - Czene, Kamila

AU - Liu, Jianjun

AU - Cox, Angela

AU - Brock, Ian W.

AU - Cross, Simon S.

AU - Reed, Malcolm W.R.

AU - Ahmed, Shahana

AU - Ghoussaini, Maya

AU - Pharoah, Paul DP

AU - Kang, Daehee

AU - Yoo, Keun Young

AU - Noh, Dong Young

AU - Jakubowska, Anna

AU - Jaworska, Katarzyna

AU - Durda, Katarzyna

AU - Złowocka, Elzbieta

AU - Sangrajrang, Suleeporn

AU - Gaborieau, Valerie

AU - Brennan, Paul

AU - McKay, James

AU - Shen, Chen Yang

AU - Yu, Jyh Cherng

AU - Hsu, Huan Ming

AU - Hou, Ming Feng

AU - Orr, Nick

AU - Schoemaker, Minouk

AU - Ashworth, Alan

AU - Swerdlow, Anthony

AU - Trentham-Dietz, Amy

AU - Newcomb, Polly A.

AU - Titus, Linda

AU - Egan, Kathleen M.

AU - Chenevix-Trench, Georgia

AU - Antoniou, Antonis C.

AU - Humphreys, Manjeet K.

AU - Morrison, Jonathan

AU - Chang-Claude, Jenny

AU - Easton, Douglas F.

AU - Dunning, Alison M.

PY - 2012/8/7

Y1 - 2012/8/7

N2 - The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6×10-14 in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8×10-18 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2×10-9 in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8×10-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8×10-17 versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3×10-7, pheterogeneity = 5.1×10-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.

AB - The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6×10-14 in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8×10-18 in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2×10-9 in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8×10-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8×10-17 versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3×10-7, pheterogeneity = 5.1×10-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.

UR - http://www.scopus.com/inward/record.url?scp=84865061552&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0042380

DO - 10.1371/journal.pone.0042380

M3 - Article

C2 - 22879957

AN - SCOPUS:84865061552

SN - 1932-6203

VL - 7

JO - PLoS ONE

JF - PLoS ONE

IS - 8

M1 - e42380

ER -

Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)

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