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Breast Cancer Risk and 6q22.33: Combined Results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2

Kirchhoff, Tomas; Gaudet, Mia M.; Antoniou, Antonis C.; McGuffog, Lesley; Humphreys, Manjeet K.; Dunning, Alison M.; Bojesen, Stig E.; Nordestgaard, Borge G.; Flyger, Henrik and Kang, Daehee, et al. (2012) In PLoS ONE 7(6).
Abstract
Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak... (More)
Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I-2 = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95% CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk. (Less)
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6
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Public Library of Science
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  • scopus:84863215020
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1932-6203
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10.1371/journal.pone.0035706
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English
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@article{ba0e7816-d120-48a7-8df2-0edece3a8a76,
  abstract     = {Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I-2 = 49.3%; p = &lt;0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95% CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.},
  author       = {Kirchhoff, Tomas and Gaudet, Mia M. and Antoniou, Antonis C. and McGuffog, Lesley and Humphreys, Manjeet K. and Dunning, Alison M. and Bojesen, Stig E. and Nordestgaard, Borge G. and Flyger, Henrik and Kang, Daehee and Yoo, Keun-Young and Noh, Dong-Young and Ahn, Sei-Hyun and Dork, Thilo and Schuermann, Peter and Karstens, Johann H. and Hillemanns, Peter and Couch, Fergus J. and Olson, Janet and Vachon, Celine and Wang, Xianshu and Cox, Angela and Brock, Ian and Elliott, Graeme and Reed, Malcolm W. R. and Burwinkel, Barbara and Meindl, Alfons and Brauch, Hiltrud and Hamann, Ute and Ko, Yon-Dschun and Broeks, Annegien and Schmidt, Marjanka K. and Van 't Veer, Laura J. and Braaf, Linde M. and Johnson, Nichola and Fletcher, Olivia and Gibson, Lorna and Peto, Julian and Turnbull, Clare and Seal, Sheila and Renwick, Anthony and Rahman, Nazneen and Wu, Pei-Ei and Yu, Jyh-Cherng and Hsiung, Chia-Ni and Shen, Chen-Yang and Southey, Melissa C. and Hopper, John L. and Hammet, Fleur and Van Dorpe, Thijs and Dieudonne, Anne-Sophie and Hatse, Sigrid and Lambrechts, Diether and Andrulis, Irene L. and Bogdanova, Natalia and Antonenkova, Natalia and Rogov, Juri I. and Prokofieva, Daria and Bermisheva, Marina and Khusnutdinova, Elza and van Asperen, Christi J. and Tollenaar, Robert A. E. M. and Hooning, Maartje J. and Devilee, Peter and Margolin, Sara and Lindblom, Annika and Milne, Roger L. and Ignacio Arias, Jose and Pilar Zamora, M. and Benitez, Javier and Severi, Gianluca and Baglietto, Laura and Giles, Graham G. and Spurdle, Amanda B. and Beesley, Jonathan and Chen, Xiaoqing and Holland, Helene and Healey, Sue and Wang-Gohrke, Shan and Chang-Claude, Jenny and Mannermaa, Arto and Kosma, Veli-Matti and Kauppinen, Jaana and Kataja, Vesa and Agnarsson, Bjarni A. and Caligo, Maria A. and Godwin, Andrew K. and Nevanlinna, Heli and Heikkinen, Tuomas and Fredericksen, Zachary and Lindor, Noralane and Nathanson, Katherine L. and Domchek, Susan M. and Loman, Niklas and Karlsson, Per and Askmalm, Marie Stenmark and Melin, Beatrice and von Wachenfeldt, Anna and Hogervorst, Frans B. L. and Verheus, Martijn and Rookus, Matti A. and Seynaeve, Caroline and Oldenburg, Rogier A. and Ligtenberg, Marjolijn J. and Ausems, Margreet G. E. M. and Aalfs, Cora M. and Gille, Hans J. P. and Wijnen, Juul T. and Garcia, Encarna B. Gomez and Peock, Susan and Cook, Margaret and Oliver, Clare T. and Frost, Debra and Luccarini, Craig and Pichert, Gabriella and Davidson, Rosemarie and Chu, Carol and Eccles, Diana and Ong, Kai-Ren and Cook, Jackie and Douglas, Fiona and Hodgson, Shirley and Evans, D. Gareth and Eeles, Rosalind and Gold, Bert and Pharoah, Paul D. P. and Offit, Kenneth and Chenevix-Trench, Georgia and Easton, Douglas F.},
  issn         = {1932-6203},
  language     = {eng},
  number       = {6},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Breast Cancer Risk and 6q22.33: Combined Results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2},
  url          = {http://dx.doi.org/10.1371/journal.pone.0035706},
  volume       = {7},
  year         = {2012},
}