Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

R Hein; M Maranian; J L Hopper; M K Kapuscinski; M C Southey; D J Park; M K Schmidt; A Broeks; F B Hogervorst; H B Bueno-de-Mesquit; K R Muir; A Lophatananon; S Rattanamongkongul; P Puttawibul; P A Fasching; A Hein; A B Ekici; M W Beckmann; O Fletcher; N Johnson; I dos Santos Silva; J Peto; E Sawyer; I Tomlinson; M Kerin; N Miller; F Marmee; A Schneeweiss; C Sohn; B Burwinkel; P Guenel; E Cordina-Duverger; F Menegaux; T Truong; S E Bojesen; B G Nordestgaard; H Flyger; R L Milne; J I Perez; M P Zamora; J Benitez; H Anton-Culver; A Ziogas; L Bernstein; C A Clarke; H Brenner; H Muller; V Arndt; C Stegmaier; N Rahman; S Seal; C Turnbull; A Renwick; A Meindl; S Schott; C R Bartram; R K Schmutzler; H Brauch; U Hamann; Y D Ko; S Wang-Gohrke; T Dork; P Schurmann; J H Karstens; P Hillemanns; H Nevanlinna; T Heikkinen; K Aittomaki; C Blomqvist; N V Bogdanova; I V Zalutsky; N N Antonenkova; M Bermisheva; D Prokovieva; A Farahtdinova; E Khusnutdinova; A Lindblom; S Margolin; A Mannermaa; V Kataja; V M Kosma; J Hartikainen; X Chen; J Beesley; D Lambrechts; H Zhao; P Neven; H Wildiers; S Nickels; D Flesch-Janys; P Radice; P Peterlongo; S Manoukian; M Barile; F J Couch; J E Olson; X Wang; Z Fredericksen; G G Giles; L Baglietto; C A McLean; G Severi; K Offit; M Robson; M M Gaudet; J Vijai; G G Alnaes; V Kristensen; A L Borresen-Dale; E M John; A Miron; R Winqvist; K Pylkas; A Jukkola-Vuorinen; M Grip; I L Andrulis; J A Knight; G Glendon; A M Mulligan; J D Figueroa; M Garcia-Closas; J Lissowska; M E Sherman; M Hooning; J W Martens; C Seynaeve; M Collee; P Hall; K Humpreys; K Czene; J Liu; A Cox; I W Brock; S S Cross; M W Reed; S Ahmed; M Ghoussaini; P D Pharoah; D Kang; K Y Yoo; D Y Noh; A Jakubowska; K Jaworska; K Durda; E Zlowocka; S Sangrajrang; V Gaborieau; P Brennan; J McKay; C Y Shen; J C Yu; H M Hsu; M F Hou; N Orr; M Schoemaker; A Ashworth; A Swerdlow; A Trentham-Dietz; P A Newcomb; L Titus; K M Egan; G Chenevix-Trench; A C Antoniou; M K Humphreys; J Morrison; J Chang-Claude; D F Easton; A 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)

R Hein, M Maranian, J L Hopper, M K Kapuscinski, M C Southey, D J Park, M K Schmidt, A Broeks, F B Hogervorst, H B Bueno-de-Mesquit, K R Muir, A Lophatananon, S Rattanamongkongul, P Puttawibul, P A Fasching, A Hein, A B Ekici, M W Beckmann, O Fletcher, N JohnsonI dos Santos Silva, J Peto, E Sawyer, I Tomlinson, M Kerin, N Miller, F Marmee, A Schneeweiss, C Sohn, B Burwinkel, P Guenel, E Cordina-Duverger, F Menegaux, T Truong, S E Bojesen, B G Nordestgaard, H Flyger, R L Milne, J I Perez, M P Zamora, J Benitez, H Anton-Culver, A Ziogas, L Bernstein, C A Clarke, H Brenner, H Muller, V Arndt, C Stegmaier, N Rahman, S Seal, C Turnbull, A Renwick, A Meindl, S Schott, C R Bartram, R K Schmutzler, H Brauch, U Hamann, Y D Ko, S Wang-Gohrke, T Dork, P Schurmann, J H Karstens, P Hillemanns, H Nevanlinna, T Heikkinen, K Aittomaki, C Blomqvist, N V Bogdanova, I V Zalutsky, N N Antonenkova, M Bermisheva, D Prokovieva, A Farahtdinova, E Khusnutdinova, A Lindblom, S Margolin, A Mannermaa, V Kataja, V M Kosma, J Hartikainen, X Chen, J Beesley, D Lambrechts, H Zhao, P Neven, H Wildiers, S Nickels, D Flesch-Janys, P Radice, P Peterlongo, S Manoukian, M Barile, F J Couch, J E Olson, X Wang, Z Fredericksen, G G Giles, L Baglietto, C A McLean, G Severi, K Offit, M Robson, M M Gaudet, J Vijai, G G Alnaes, V Kristensen, A L Borresen-Dale, E M John, A Miron, R Winqvist, K Pylkas, A Jukkola-Vuorinen, M Grip, I L Andrulis, J A Knight, G Glendon, A M Mulligan, J D Figueroa, M Garcia-Closas, J Lissowska, M E Sherman, M Hooning, J W Martens, C Seynaeve, M Collee, P Hall, K Humpreys, K Czene, J Liu, A Cox, I W Brock, S S Cross, M W Reed, S Ahmed, M Ghoussaini, P D Pharoah, D Kang, K Y Yoo, D Y Noh, A Jakubowska, K Jaworska, K Durda, E Zlowocka, S Sangrajrang, V Gaborieau, P Brennan, J McKay, C Y Shen, J C Yu, H M Hsu, M F Hou, N Orr, M Schoemaker, A Ashworth, A Swerdlow, A Trentham-Dietz, P A Newcomb, L Titus, K M Egan, G Chenevix-Trench, A C Antoniou, M K Humphreys, J Morrison, J Chang-Claude, D F Easton, A M Dunning

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

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 x 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 x 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 x 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 x 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 x 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 x 10(-7), p(heterogeneity) = 5.1 x 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
Journal	PLoS ONE
Volume	7
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0042380
Publication status	Published - 2012

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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., 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). https://doi.org/10.1371/journal.pone.0042380

@article{fa2269ee9feb467ba171fdf256b03948,

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 x 10(-14) in Asians and 1.09 (95\% CI 1.07-1.11), p = 6.8 x 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95\% CI 1.19-1.41), p = 1.2 x 10(-9) in Asians and 1.12 (95\% CI 1.08-1.17), p = 3.8 x 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 x 10(-17) versus OR (ER+) = 1.07 (95\% CI 1.04-1.1), p = 1.3 x 10(-7), p(heterogeneity) = 5.1 x 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 = "R Hein and M Maranian and Hopper, \{J L\} and Kapuscinski, \{M K\} and Southey, \{M C\} and Park, \{D J\} and Schmidt, \{M K\} and A Broeks and Hogervorst, \{F B\} and Bueno-de-Mesquit, \{H B\} and Muir, \{K R\} and A Lophatananon and S Rattanamongkongul and P Puttawibul and Fasching, \{P A\} and A Hein and Ekici, \{A B\} and Beckmann, \{M W\} and O Fletcher and N Johnson and \{dos Santos Silva\}, I and J Peto and E Sawyer and I Tomlinson and M Kerin and N Miller and F Marmee and A Schneeweiss and C Sohn and B Burwinkel and P Guenel and E Cordina-Duverger and F Menegaux and T Truong and Bojesen, \{S E\} and Nordestgaard, \{B G\} and H Flyger and Milne, \{R L\} and Perez, \{J I\} and Zamora, \{M P\} and J Benitez and H Anton-Culver and A Ziogas and L Bernstein and Clarke, \{C A\} and H Brenner and H Muller and V Arndt and C Stegmaier and N Rahman and S Seal and C Turnbull and A Renwick and A Meindl and S Schott and Bartram, \{C R\} and Schmutzler, \{R K\} and H Brauch and U Hamann and Ko, \{Y D\} and S Wang-Gohrke and T Dork and P Schurmann and Karstens, \{J H\} and P Hillemanns and H Nevanlinna and T Heikkinen and K Aittomaki and C Blomqvist and Bogdanova, \{N V\} and Zalutsky, \{I V\} and Antonenkova, \{N N\} and M Bermisheva and D Prokovieva and A Farahtdinova and E Khusnutdinova and A Lindblom and S Margolin and A Mannermaa and V Kataja and Kosma, \{V M\} and J Hartikainen and X Chen and J Beesley and D Lambrechts and H Zhao and P Neven and H Wildiers and S Nickels and D Flesch-Janys and P Radice and P Peterlongo and S Manoukian and M Barile and Couch, \{F J\} and Olson, \{J E\} and X Wang and Z Fredericksen and Giles, \{G G\} and L Baglietto and McLean, \{C A\} and G Severi and K Offit and M Robson and Gaudet, \{M M\} and J Vijai and Alnaes, \{G G\} and V Kristensen and Borresen-Dale, \{A L\} and John, \{E M\} and A Miron and R Winqvist and K Pylkas and A Jukkola-Vuorinen and M Grip and Andrulis, \{I L\} and Knight, \{J A\} and G Glendon and Mulligan, \{A M\} and Figueroa, \{J D\} and M Garcia-Closas and J Lissowska and Sherman, \{M E\} and M Hooning and Martens, \{J W\} and C Seynaeve and M Collee and P Hall and K Humpreys and K Czene and J Liu and A Cox and Brock, \{I W\} and Cross, \{S S\} and Reed, \{M W\} and S Ahmed and M Ghoussaini and Pharoah, \{P D\} and D Kang and Yoo, \{K Y\} and Noh, \{D Y\} and A Jakubowska and K Jaworska and K Durda and E Zlowocka and S Sangrajrang and V Gaborieau and P Brennan and J McKay and Shen, \{C Y\} and Yu, \{J C\} and Hsu, \{H M\} and Hou, \{M F\} and N Orr and M Schoemaker and A Ashworth and A Swerdlow and A Trentham-Dietz and Newcomb, \{P A\} and L Titus and Egan, \{K M\} and G Chenevix-Trench and Antoniou, \{A C\} and Humphreys, \{M K\} and J Morrison and J Chang-Claude and Easton, \{D F\} and Dunning, \{A M\}",

note = "Hein, Rebecca Maranian, Melanie Hopper, John L Kapuscinski, Miroslaw K Southey, Melissa C Park, Daniel J Schmidt, Marjanka K Broeks, Annegien Hogervorst, Frans B L Bueno-de-Mesquit, H Bas Muir, Kenneth R Lophatananon, Artitaya Rattanamongkongul, Suthee Puttawibul, Puttisak Fasching, Peter A Hein, Alexander Ekici, Arif B Beckmann, Matthias W Fletcher, Olivia Johnson, Nichola dos Santos Silva, Isabel Peto, Julian Sawyer, Elinor Tomlinson, Ian Kerin, Michael Miller, Nicola Marmee, Frederick Schneeweiss, Andreas Sohn, Christof Burwinkel, Barbara Guenel, Pascal Cordina-Duverger, Emilie Menegaux, Florence Truong, Therese Bojesen, Stig E Nordestgaard, Borge G Flyger, Henrik Milne, Roger L Perez, Jose Ignacio Arias Zamora, M Pilar Benitez, Javier Anton-Culver, Hoda Ziogas, Argyrios Bernstein, Leslie Clarke, Christina A Brenner, Hermann Muller, Heiko Arndt, Volker Stegmaier, Christa Rahman, Nazneen Seal, Sheila Turnbull, Clare Renwick, Anthony Meindl, Alfons Schott, Sarah Bartram, Claus R Schmutzler, Rita K Brauch, Hiltrud Hamann, Ute Ko, Yon-Dschun GENICA Network Wang-Gohrke, Shan Dork, Thilo Schurmann, Peter Karstens, Johann H Hillemanns, Peter Nevanlinna, Heli Heikkinen, Tuomas Aittomaki, Kristiina Blomqvist, Carl Bogdanova, Natalia V Zalutsky, Iosif V Antonenkova, Natalia N Bermisheva, Marina Prokovieva, Darya Farahtdinova, Albina Khusnutdinova, Elza Lindblom, Annika Margolin, Sara Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana Chen, Xiaoqing Beesley, Jonathan Kconfab Investigators AOCS Group Lambrechts, Diether Zhao, Hui Neven, Patrick Wildiers, Hans Nickels, Stefan Flesch-Janys, Dieter Radice, Paolo Peterlongo, Paolo Manoukian, Siranoush Barile, Monica Couch, Fergus J Olson, Janet E Wang, Xianshu Fredericksen, Zachary Giles, Graham G Baglietto, Laura McLean, Catriona A Severi, Gianluca Offit, Kenneth Robson, Mark Gaudet, Mia M Vijai, Joseph Alnaes, Grethe Grenaker Kristensen, Vessela Borresen-Dale, Anne-Lise John, Esther M Miron, Alexander Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi Andrulis, Irene L Knight, Julia A Glendon, Gord Mulligan, Anna Marie Figueroa, Jonine D Garcia-Closas, Montserrat Lissowska, Jolanta Sherman, Mark E Hooning, Maartje Martens, John W M Seynaeve, Caroline Collee, Margriet Hall, Per Humpreys, Keith Czene, Kamila Liu, Jianjun Cox, Angela Brock, Ian W Cross, Simon S Reed, Malcolm W R Ahmed, Shahana Ghoussaini, Maya Pharoah, Paul D P Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Jakubowska, Anna Jaworska, Katarzyna Durda, Katarzyna Zlowocka, Elzbieta Sangrajrang, Suleeporn Gaborieau, Valerie Brennan, Paul McKay, James Shen, Chen-Yang Yu, Jyh-Cherng Hsu, Huan-Ming Hou, Ming-Feng Orr, Nick Schoemaker, Minouk Ashworth, Alan Swerdlow, Anthony Trentham-Dietz, Amy Newcomb, Polly A Titus, Linda Egan, Kathleen M Chenevix-Trench, Georgia Antoniou, Antonis C Humphreys, Manjeet K Morrison, Jonathan Chang-Claude, Jenny Easton, Douglas F Dunning, Alison M C1287/A10118/Cancer Research UK/United Kingdom C1287/A12014/Cancer Research UK/United Kingdom C490/A11021/Cancer Research UK/United Kingdom C8197/A10123/Cancer Research UK/United Kingdom C8197/A10865/Cancer Research UK/United Kingdom C8620/A8372/Cancer Research UK/United Kingdom C8620/A8857/Cancer Research UK/United Kingdom CA116201/CA/NCI NIH HHS/United States CA58860/CA/NCI NIH HHS/United States CA92044/CA/NCI NIH HHS/United States R01 CA128978/CA/NCI NIH HHS/United States R01 CA47147/CA/NCI NIH HHS/United States R01 CA77398/CA/NCI NIH HHS/United States R01CA122340/CA/NCI NIH HHS/United States R01CA47305/CA/NCI NIH HHS/United States R01CA69664/CA/NCI NIH HHS/United States RFA \# CA- 06-503/CA/NCI NIH HHS/United States RFA-CA-06-503/CA/NCI NIH HHS/United States U01 CA69417/CA/NCI NIH HHS/United States U01 CA69467/CA/NCI NIH HHS/United States U01 CA69638/CA/NCI NIH HHS/United States Medical Research Council/United Kingdom Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States PloS one PLoS One. 2012;7(8):e42380. Epub 2012 Aug 7.",

year = "2012",

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

language = "English",

volume = "7",

journal = "PLoS ONE",

publisher = "Public Library of Science",

number = "8",

}

Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, MK, Broeks, A, Hogervorst, FB, 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, Guenel, P, Cordina-Duverger, E, Menegaux, F, Truong, T, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, RL, Perez, JI, Zamora, MP, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Muller, 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, Dork, T, Schurmann, P, Karstens, JH, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomaki, 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, Alnaes, GG, Kristensen, V, Borresen-Dale, AL, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Figueroa, JD, Garcia-Closas, M, Lissowska, J, Sherman, ME, Hooning, M, Martens, JW, Seynaeve, C, Collee, M, Hall, P, Humpreys, K, Czene, K, Liu, J, Cox, A, Brock, IW, Cross, SS, Reed, MW, Ahmed, S, Ghoussaini, M, Pharoah, PD, Kang, D, Yoo, KY, Noh, DY, Jakubowska, A, Jaworska, K, Durda, K, Zlowocka, 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. 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, R

AU - Maranian, M

AU - Hopper, J L

AU - Kapuscinski, M K

AU - Southey, M C

AU - Park, D J

AU - Schmidt, M K

AU - Broeks, A

AU - Hogervorst, F B

AU - Bueno-de-Mesquit, H B

AU - Muir, K R

AU - Lophatananon, A

AU - Rattanamongkongul, S

AU - Puttawibul, P

AU - Fasching, P A

AU - Hein, A

AU - Ekici, A B

AU - Beckmann, M W

AU - Fletcher, O

AU - Johnson, N

AU - dos Santos Silva, I

AU - Peto, J

AU - Sawyer, E

AU - Tomlinson, I

AU - Kerin, M

AU - Miller, N

AU - Marmee, F

AU - Schneeweiss, A

AU - Sohn, C

AU - Burwinkel, B

AU - Guenel, P

AU - Cordina-Duverger, E

AU - Menegaux, F

AU - Truong, T

AU - Bojesen, S E

AU - Nordestgaard, B G

AU - Flyger, H

AU - Milne, R L

AU - Perez, J I

AU - Zamora, M P

AU - Benitez, J

AU - Anton-Culver, H

AU - Ziogas, A

AU - Bernstein, L

AU - Clarke, C A

AU - Brenner, H

AU - Muller, H

AU - Arndt, V

AU - Stegmaier, C

AU - Rahman, N

AU - Seal, S

AU - Turnbull, C

AU - Renwick, A

AU - Meindl, A

AU - Schott, S

AU - Bartram, C R

AU - Schmutzler, R K

AU - Brauch, H

AU - Hamann, U

AU - Ko, Y D

AU - Wang-Gohrke, S

AU - Dork, T

AU - Schurmann, P

AU - Karstens, J H

AU - Hillemanns, P

AU - Nevanlinna, H

AU - Heikkinen, T

AU - Aittomaki, K

AU - Blomqvist, C

AU - Bogdanova, N V

AU - Zalutsky, I V

AU - Antonenkova, N N

AU - Bermisheva, M

AU - Prokovieva, D

AU - Farahtdinova, A

AU - Khusnutdinova, E

AU - Lindblom, A

AU - Margolin, S

AU - Mannermaa, A

AU - Kataja, V

AU - Kosma, V M

AU - Hartikainen, J

AU - Chen, X

AU - Beesley, J

AU - Lambrechts, D

AU - Zhao, H

AU - Neven, P

AU - Wildiers, H

AU - Nickels, S

AU - Flesch-Janys, D

AU - Radice, P

AU - Peterlongo, P

AU - Manoukian, S

AU - Barile, M

AU - Couch, F J

AU - Olson, J E

AU - Wang, X

AU - Fredericksen, Z

AU - Giles, G G

AU - Baglietto, L

AU - McLean, C A

AU - Severi, G

AU - Offit, K

AU - Robson, M

AU - Gaudet, M M

AU - Vijai, J

AU - Alnaes, G G

AU - Kristensen, V

AU - Borresen-Dale, A L

AU - John, E M

AU - Miron, A

AU - Winqvist, R

AU - Pylkas, K

AU - Jukkola-Vuorinen, A

AU - Grip, M

AU - Andrulis, I L

AU - Knight, J A

AU - Glendon, G

AU - Mulligan, A M

AU - Figueroa, J D

AU - Garcia-Closas, M

AU - Lissowska, J

AU - Sherman, M E

AU - Hooning, M

AU - Martens, J W

AU - Seynaeve, C

AU - Collee, M

AU - Hall, P

AU - Humpreys, K

AU - Czene, K

AU - Liu, J

AU - Cox, A

AU - Brock, I W

AU - Cross, S S

AU - Reed, M W

AU - Ahmed, S

AU - Ghoussaini, M

AU - Pharoah, P D

AU - Kang, D

AU - Yoo, K Y

AU - Noh, D Y

AU - Jakubowska, A

AU - Jaworska, K

AU - Durda, K

AU - Zlowocka, E

AU - Sangrajrang, S

AU - Gaborieau, V

AU - Brennan, P

AU - McKay, J

AU - Shen, C Y

AU - Yu, J C

AU - Hsu, H M

AU - Hou, M F

AU - Orr, N

AU - Schoemaker, M

AU - Ashworth, A

AU - Swerdlow, A

AU - Trentham-Dietz, A

AU - Newcomb, P A

AU - Titus, L

AU - Egan, K M

AU - Chenevix-Trench, G

AU - Antoniou, A C

AU - Humphreys, M K

AU - Morrison, J

AU - Chang-Claude, J

AU - Easton, D F

AU - Dunning, A M

N1 - Hein, Rebecca Maranian, Melanie Hopper, John L Kapuscinski, Miroslaw K Southey, Melissa C Park, Daniel J Schmidt, Marjanka K Broeks, Annegien Hogervorst, Frans B L Bueno-de-Mesquit, H Bas Muir, Kenneth R Lophatananon, Artitaya Rattanamongkongul, Suthee Puttawibul, Puttisak Fasching, Peter A Hein, Alexander Ekici, Arif B Beckmann, Matthias W Fletcher, Olivia Johnson, Nichola dos Santos Silva, Isabel Peto, Julian Sawyer, Elinor Tomlinson, Ian Kerin, Michael Miller, Nicola Marmee, Frederick Schneeweiss, Andreas Sohn, Christof Burwinkel, Barbara Guenel, Pascal Cordina-Duverger, Emilie Menegaux, Florence Truong, Therese Bojesen, Stig E Nordestgaard, Borge G Flyger, Henrik Milne, Roger L Perez, Jose Ignacio Arias Zamora, M Pilar Benitez, Javier Anton-Culver, Hoda Ziogas, Argyrios Bernstein, Leslie Clarke, Christina A Brenner, Hermann Muller, Heiko Arndt, Volker Stegmaier, Christa Rahman, Nazneen Seal, Sheila Turnbull, Clare Renwick, Anthony Meindl, Alfons Schott, Sarah Bartram, Claus R Schmutzler, Rita K Brauch, Hiltrud Hamann, Ute Ko, Yon-Dschun GENICA Network Wang-Gohrke, Shan Dork, Thilo Schurmann, Peter Karstens, Johann H Hillemanns, Peter Nevanlinna, Heli Heikkinen, Tuomas Aittomaki, Kristiina Blomqvist, Carl Bogdanova, Natalia V Zalutsky, Iosif V Antonenkova, Natalia N Bermisheva, Marina Prokovieva, Darya Farahtdinova, Albina Khusnutdinova, Elza Lindblom, Annika Margolin, Sara Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Hartikainen, Jaana Chen, Xiaoqing Beesley, Jonathan Kconfab Investigators AOCS Group Lambrechts, Diether Zhao, Hui Neven, Patrick Wildiers, Hans Nickels, Stefan Flesch-Janys, Dieter Radice, Paolo Peterlongo, Paolo Manoukian, Siranoush Barile, Monica Couch, Fergus J Olson, Janet E Wang, Xianshu Fredericksen, Zachary Giles, Graham G Baglietto, Laura McLean, Catriona A Severi, Gianluca Offit, Kenneth Robson, Mark Gaudet, Mia M Vijai, Joseph Alnaes, Grethe Grenaker Kristensen, Vessela Borresen-Dale, Anne-Lise John, Esther M Miron, Alexander Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi Andrulis, Irene L Knight, Julia A Glendon, Gord Mulligan, Anna Marie Figueroa, Jonine D Garcia-Closas, Montserrat Lissowska, Jolanta Sherman, Mark E Hooning, Maartje Martens, John W M Seynaeve, Caroline Collee, Margriet Hall, Per Humpreys, Keith Czene, Kamila Liu, Jianjun Cox, Angela Brock, Ian W Cross, Simon S Reed, Malcolm W R Ahmed, Shahana Ghoussaini, Maya Pharoah, Paul D P Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Jakubowska, Anna Jaworska, Katarzyna Durda, Katarzyna Zlowocka, Elzbieta Sangrajrang, Suleeporn Gaborieau, Valerie Brennan, Paul McKay, James Shen, Chen-Yang Yu, Jyh-Cherng Hsu, Huan-Ming Hou, Ming-Feng Orr, Nick Schoemaker, Minouk Ashworth, Alan Swerdlow, Anthony Trentham-Dietz, Amy Newcomb, Polly A Titus, Linda Egan, Kathleen M Chenevix-Trench, Georgia Antoniou, Antonis C Humphreys, Manjeet K Morrison, Jonathan Chang-Claude, Jenny Easton, Douglas F Dunning, Alison M C1287/A10118/Cancer Research UK/United Kingdom C1287/A12014/Cancer Research UK/United Kingdom C490/A11021/Cancer Research UK/United Kingdom C8197/A10123/Cancer Research UK/United Kingdom C8197/A10865/Cancer Research UK/United Kingdom C8620/A8372/Cancer Research UK/United Kingdom C8620/A8857/Cancer Research UK/United Kingdom CA116201/CA/NCI NIH HHS/United States CA58860/CA/NCI NIH HHS/United States CA92044/CA/NCI NIH HHS/United States R01 CA128978/CA/NCI NIH HHS/United States R01 CA47147/CA/NCI NIH HHS/United States R01 CA77398/CA/NCI NIH HHS/United States R01CA122340/CA/NCI NIH HHS/United States R01CA47305/CA/NCI NIH HHS/United States R01CA69664/CA/NCI NIH HHS/United States RFA # CA- 06-503/CA/NCI NIH HHS/United States RFA-CA-06-503/CA/NCI NIH HHS/United States U01 CA69417/CA/NCI NIH HHS/United States U01 CA69467/CA/NCI NIH HHS/United States U01 CA69638/CA/NCI NIH HHS/United States Medical Research Council/United Kingdom Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States PloS one PLoS One. 2012;7(8):e42380. Epub 2012 Aug 7.

PY - 2012

Y1 - 2012

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 x 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 x 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 x 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 x 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 x 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 x 10(-7), p(heterogeneity) = 5.1 x 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 x 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 x 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 x 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 x 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 x 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 x 10(-7), p(heterogeneity) = 5.1 x 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.

U2 - 10.1371/journal.pone.0042380

DO - 10.1371/journal.pone.0042380

M3 - Article

VL - 7

JO - PLoS ONE

JF - PLoS ONE

IS - 8

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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