7q21-rs6964587 and breast cancer risk: An extended case-control study by the Breast Cancer Association Consortium

Roger L. Milne, Justo Lorenzo-Bermejo, Barbara Burwinkel, Núria Malats, Jose Ignacio Arias, M. Pilar Zamora, Javier Benítez, Manjeet K. Humphreys, Montserrat García-Closas, Stephen J. Chanock, Jolanta Lissowska, Mark E. Sherman, Arto Mannermaa, Vesa Kataja, Veli Matti Kosma, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Hoda Anton-CulverArgyrios Ziogas, Peter Devilee, Christie J. van Asperen, Rob A.E.M. Tollenaar, Caroline Seynaeve, Per Hall, Kamila Czene, Jianjun Liu, Astrid K. Irwanto, Daehee Kang, Keun Young Yoo, Dong Young Noh, Fergus J. Couch, Janet E. Olson, Xianshu Wang, Zachary Fredericksen, Børge G. Nordestgaard, Stig E. Bojesen, Henrik Flyger, Sara Margolin, Annika Lindblom, Peter A. Fasching, Ruediger Schulz-Wendtland, Arif B. Ekici, Matthias W. Beckmann, Shan Wang-Gohrke, Chen Yang Shen, Jyh Cherng Yu, Huan Ming Hsu, Pei Ei Wu, Graham G. Giles, Gianluca Severi, Laura Baglietto, Dallas R. English, Angela Cox, Ian Brock, Graeme Elliott, Malcolm W.R. Reed, Jonathan Beesley, Xiaoqing Chen, Olivia Fletcher, Lorna Gibson, Isabel dos Santos Silva, Julian Peto, Bernd Frank, Joerg Heil, Alfons Meindl, Jenny Chang-Claude, Rebecca Hein, Alina Vrieling, Dieter Flesch-Janys, Melissa C. Southey, Letitia Smith, Carmel Apicella, John L. Hopper, Alison M. Dunning, Karen A. Pooley, Paul D.P. Pharoah, Ute Hamann, Beate Pesch, Yon Dschun Ko, Douglas F. Easton, Georgia Chenevix-Trench

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background Using the Breast Cancer Association Consortium, the authors previously reported that the single nucleotide polymorphism 7q21-rs6964587 (AKAP9-M463I) is associated with breast cancer risk. The authors have now assessed this association more comprehensively using 16 independent case-control studies. Methods The authors genotyped 14 843 invasive case patients and 19 852 control subjects with white European ancestry and 2595 invasive case patients and 2192 control subjects with Asian ancestry. ORs were estimated by logistic regression, adjusted for study. Heterogeneity in ORs was assessed by fitting interaction terms or by subclassifying case patients and applying polytomous logistic regression. Results For white European women, the minor T allele of 7q21-rs6964587 was associated with breast cancer risk under a recessive model (OR 1.07, 95% CI 1.00 to 1.13, p=0.04). Results were inconclusive for Asian women. From a combined analysis of 24 154 case patients and 33 376 control subjects of white European ancestry from the present and previous series, the best-fitting model was recessive, with an estimated OR of 1.08 (95% CI 1.03 to 1.13, p=0.001). The OR was greater at younger ages (p trend=0.01). Conclusion This may be the first common susceptibility allele for breast cancer to be identified with a recessive mode of inheritance.

Original languageEnglish (US)
Pages (from-to)698-702
Number of pages5
JournalJournal of medical genetics
Issue number10
StatePublished - Oct 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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