Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)
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 Europea...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2012
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| _version_ | 1826269197738442752 |
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| author | Hein, R Maranian, M Hopper, J Kapuscinski, M Southey, M Park, D Schmidt, M Broeks, A Hogervorst, F Bueno-De-Mesquita, H Bueno-De-Mesquit, H Muir, K Lophatananon, A Rattanamongkongul, S Puttawibul, P Fasching, P Hein, A Ekici, AB Beckmann, M 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, R Perez, J Zamora, M Benítez, J Anton-Culver, H Ziogas, A Bernstein, L Clarke, C Brenner, H Müller, H Arndt, V Stegmaier, C Rahman, N Seal, S Turnbull, C Renwick, A Meindl, A Schott, S Bartram, C Schmutzler, R Brauch, H Hamann, U Ko, Y Wang-Gohrke, S Dörk, T Schürmann, P Karstens, J Hillemanns, P Nevanlinna, H Heikkinen, T Aittomäki, K Blomqvist, C Bogdanova, N Zalutsky, I Antonenkova, N Bermisheva, M Prokovieva, D Farahtdinova, A Khusnutdinova, E Lindblom, A Margolin, S Mannermaa, A Kataja, V Kosma, V 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, F Olson, J Wang, X Fredericksen, Z Giles, G Baglietto, L McLean, C Severi, G Offit, K Robson, M Gaudet, M Vijai, J Alnæs, G Kristensen, V Børresen-Dale, A John, E Miron, A Winqvist, R Pylkäs, K Jukkola-Vuorinen, A Grip, M Andrulis, I Knight, J Glendon, G Mulligan, A Figueroa, J García-Closas, M Lissowska, J Sherman, M Hooning, M Martens, J Seynaeve, C Collée, M Hall, P Humpreys, K Czene, K Liu, J Cox, A Brock, I Cross, S Reed, M Ahmed, S Ghoussaini, M Pharoah, P Kang, D Yoo, K Noh, D Jakubowska, A Jaworska, K Durda, K Złowocka, E Sangrajrang, S Gaborieau, V Brennan, P McKay, J Shen, C Yu, J Hsu, H Hou, M Orr, N Schoemaker, M Ashworth, A Swerdlow, A Trentham-Dietz, A Newcomb, P Titus, L Egan, K Chenevix-Trench, G Antoniou, A Humphreys, M Morrison, J Chang-Claude, J Easton, D Dunning, A |
| author_facet | Hein, R Maranian, M Hopper, J Kapuscinski, M Southey, M Park, D Schmidt, M Broeks, A Hogervorst, F Bueno-De-Mesquita, H Bueno-De-Mesquit, H Muir, K Lophatananon, A Rattanamongkongul, S Puttawibul, P Fasching, P Hein, A Ekici, AB Beckmann, M 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, R Perez, J Zamora, M Benítez, J Anton-Culver, H Ziogas, A Bernstein, L Clarke, C Brenner, H Müller, H Arndt, V Stegmaier, C Rahman, N Seal, S Turnbull, C Renwick, A Meindl, A Schott, S Bartram, C Schmutzler, R Brauch, H Hamann, U Ko, Y Wang-Gohrke, S Dörk, T Schürmann, P Karstens, J Hillemanns, P Nevanlinna, H Heikkinen, T Aittomäki, K Blomqvist, C Bogdanova, N Zalutsky, I Antonenkova, N Bermisheva, M Prokovieva, D Farahtdinova, A Khusnutdinova, E Lindblom, A Margolin, S Mannermaa, A Kataja, V Kosma, V 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, F Olson, J Wang, X Fredericksen, Z Giles, G Baglietto, L McLean, C Severi, G Offit, K Robson, M Gaudet, M Vijai, J Alnæs, G Kristensen, V Børresen-Dale, A John, E Miron, A Winqvist, R Pylkäs, K Jukkola-Vuorinen, A Grip, M Andrulis, I Knight, J Glendon, G Mulligan, A Figueroa, J García-Closas, M Lissowska, J Sherman, M Hooning, M Martens, J Seynaeve, C Collée, M Hall, P Humpreys, K Czene, K Liu, J Cox, A Brock, I Cross, S Reed, M Ahmed, S Ghoussaini, M Pharoah, P Kang, D Yoo, K Noh, D Jakubowska, A Jaworska, K Durda, K Złowocka, E Sangrajrang, S Gaborieau, V Brennan, P McKay, J Shen, C Yu, J Hsu, H Hou, M Orr, N Schoemaker, M Ashworth, A Swerdlow, A Trentham-Dietz, A Newcomb, P Titus, L Egan, K Chenevix-Trench, G Antoniou, A Humphreys, M Morrison, J Chang-Claude, J Easton, D Dunning, A |
| author_sort | Hein, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:21:17Z |
| format | Journal article |
| id | oxford-uuid:418887bf-01ce-4452-82a6-2dc6ab30d5d8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:21:17Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:418887bf-01ce-4452-82a6-2dc6ab30d5d82022-03-26T14:44:42ZComparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:418887bf-01ce-4452-82a6-2dc6ab30d5d8EnglishSymplectic Elements at OxfordPublic Library of Science2012Hein, RMaranian, MHopper, JKapuscinski, MSouthey, MPark, DSchmidt, MBroeks, AHogervorst, FBueno-De-Mesquita, HBueno-De-Mesquit, HMuir, KLophatananon, ARattanamongkongul, SPuttawibul, PFasching, PHein, AEkici, ABBeckmann, MFletcher, OJohnson, NDos Santos Silva, IPeto, JSawyer, ETomlinson, IKerin, MMiller, NMarmee, FSchneeweiss, ASohn, CBurwinkel, BGuénel, PCordina-Duverger, EMenegaux, FTruong, TBojesen, SENordestgaard, BGFlyger, HMilne, RPerez, JZamora, MBenítez, JAnton-Culver, HZiogas, ABernstein, LClarke, CBrenner, HMüller, HArndt, VStegmaier, CRahman, NSeal, STurnbull, CRenwick, AMeindl, ASchott, SBartram, CSchmutzler, RBrauch, HHamann, UKo, YWang-Gohrke, SDörk, TSchürmann, PKarstens, JHillemanns, PNevanlinna, HHeikkinen, TAittomäki, KBlomqvist, CBogdanova, NZalutsky, IAntonenkova, NBermisheva, MProkovieva, DFarahtdinova, AKhusnutdinova, ELindblom, AMargolin, SMannermaa, AKataja, VKosma, VHartikainen, JChen, XBeesley, JLambrechts, DZhao, HNeven, PWildiers, HNickels, SFlesch-Janys, DRadice, PPeterlongo, PManoukian, SBarile, MCouch, FOlson, JWang, XFredericksen, ZGiles, GBaglietto, LMcLean, CSeveri, GOffit, KRobson, MGaudet, MVijai, JAlnæs, GKristensen, VBørresen-Dale, AJohn, EMiron, AWinqvist, RPylkäs, KJukkola-Vuorinen, AGrip, MAndrulis, IKnight, JGlendon, GMulligan, AFigueroa, JGarcía-Closas, MLissowska, JSherman, MHooning, MMartens, JSeynaeve, CCollée, MHall, PHumpreys, KCzene, KLiu, JCox, ABrock, ICross, SReed, MAhmed, SGhoussaini, MPharoah, PKang, DYoo, KNoh, DJakubowska, AJaworska, KDurda, KZłowocka, ESangrajrang, SGaborieau, VBrennan, PMcKay, JShen, CYu, JHsu, HHou, MOrr, NSchoemaker, MAshworth, ASwerdlow, ATrentham-Dietz, ANewcomb, PTitus, LEgan, KChenevix-Trench, GAntoniou, AHumphreys, MMorrison, JChang-Claude, JEaston, DDunning, AThe 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. |
| spellingShingle | Hein, R Maranian, M Hopper, J Kapuscinski, M Southey, M Park, D Schmidt, M Broeks, A Hogervorst, F Bueno-De-Mesquita, H Bueno-De-Mesquit, H Muir, K Lophatananon, A Rattanamongkongul, S Puttawibul, P Fasching, P Hein, A Ekici, AB Beckmann, M 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, R Perez, J Zamora, M Benítez, J Anton-Culver, H Ziogas, A Bernstein, L Clarke, C Brenner, H Müller, H Arndt, V Stegmaier, C Rahman, N Seal, S Turnbull, C Renwick, A Meindl, A Schott, S Bartram, C Schmutzler, R Brauch, H Hamann, U Ko, Y Wang-Gohrke, S Dörk, T Schürmann, P Karstens, J Hillemanns, P Nevanlinna, H Heikkinen, T Aittomäki, K Blomqvist, C Bogdanova, N Zalutsky, I Antonenkova, N Bermisheva, M Prokovieva, D Farahtdinova, A Khusnutdinova, E Lindblom, A Margolin, S Mannermaa, A Kataja, V Kosma, V 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, F Olson, J Wang, X Fredericksen, Z Giles, G Baglietto, L McLean, C Severi, G Offit, K Robson, M Gaudet, M Vijai, J Alnæs, G Kristensen, V Børresen-Dale, A John, E Miron, A Winqvist, R Pylkäs, K Jukkola-Vuorinen, A Grip, M Andrulis, I Knight, J Glendon, G Mulligan, A Figueroa, J García-Closas, M Lissowska, J Sherman, M Hooning, M Martens, J Seynaeve, C Collée, M Hall, P Humpreys, K Czene, K Liu, J Cox, A Brock, I Cross, S Reed, M Ahmed, S Ghoussaini, M Pharoah, P Kang, D Yoo, K Noh, D Jakubowska, A Jaworska, K Durda, K Złowocka, E Sangrajrang, S Gaborieau, V Brennan, P McKay, J Shen, C Yu, J Hsu, H Hou, M Orr, N Schoemaker, M Ashworth, A Swerdlow, A Trentham-Dietz, A Newcomb, P Titus, L Egan, K Chenevix-Trench, G Antoniou, A Humphreys, M Morrison, J Chang-Claude, J Easton, D Dunning, A Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC) |
| title | Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC) |
| title_full | Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC) |
| title_fullStr | Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC) |
| title_full_unstemmed | Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC) |
| title_short | Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC) |
| title_sort | 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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comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT gilesg comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT bagliettol comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT mcleanc comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT severig comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT offitk comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT robsonm comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT gaudetm 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comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT nohd comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT jakubowskaa comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT jaworskak comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT durdak comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT złowockae comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT sangrajrangs comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac AT gaborieauv 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comparisonof6q25breastcancerhitsfromasianandeuropeangenomewideassociationstudiesinthebreastcancerassociationconsortiumbcac |