Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk

K. N. Stevens, Montserrat Garcia-Closas, Zachary Fredericksen, Matthew Kosel, V. Shane Pankratz, J. L. Hopper, Gillian S Dite, Carmel Apicella, M. C. Southey, M. K. Schmidt, Annegien Broeks, Laura J Van 't Veer, R A E M Tollenaar, Peter A. Fasching, Matthias W. Beckmann, Alexander Hein, Arif B Ekici, N. Johnson, Julian Peto, I. Dos Santos SilvaJohn L Gibson, Edward Sawyer, Ian P Tomlinson, Michael J. Kerin, Stephen J Chanock, Jolanta Lissowska, D. J. Hunter, Robert N Hoover, G. D. Thomas, R. L. Milne, Ji Arias Pérez, A. González-Neira, J. Benítez, Barbara Burwinkel, Alfons Meindl, Rita K. Schmutzler, C. R. Bartrar, Ute Hamann, Yon-Dschun Ko, T. Brüning, Jenny Chang-Claude, R. Hein, Shan Wang-Gohrke, Dörk Thilo Dörk, Peter Schürmann, Michael Bremer, Peter Hillemanns, Natalia Bogdanova, J. V. Zalutsky, Yuri I. Rogov, Natalia Antonenkova, Annika Lindblom, Sara Margolin, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Juha Hartikainen, Georgia Chenevix-Trench, X. Chen, Paolo Peterlongo, Bernardo Bonanni, Laetitia Bernard, Siranoush Manoukian, X. Wang, James R. Cerhan, Celine M Vachon, Janet E Olson, G. G. Giles, Laura Baglietto, C. A. McLean, Gianluca Severi, Esther M. John, Alexander Miron, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L Andrulis, J. A. Knight, Grodon Glendon, Anna M.arie Mulligan, A. Cox, Ian W. Brock, Thomas G Elliott, S. S. Cross, Paul D P Pharoah, A. M. Dunning, Karen A Pooley, M. K. Humphreys, J. Wang, Deying Kang, Keun-Young Yoo, Dong-Young Noh, Suleeporn Sangrajrang, V. Gabrieau, P Brennan, J. McKay, Hoda Anton-Culver, A K Ziogas, Fergus J Couch, Doug F. Easton

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Abstract

Background: Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer. Methods: A single-nucleotide polymorphism from the PIK3CA locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC). Results: Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR)=0.97, 95% confidence interval (CI) 0.95-0.99, P=4.6 × 10 3), but did not reach significance in the BCAC replication study alone (OR=0.98, 95% CI 0.96-1.01, P=0.139).Conclusion: Common germline variation in PIK3CA does not have a strong influence on the risk of breast cancer.

Original languageEnglish
Pages (from-to)1934-1939
Number of pages6
JournalBritish Journal of Cancer
Volume105
Issue number12
DOIs
Publication statusPublished - 6 Dec 2011
Externally publishedYes

Keywords

  • Association study
  • Genetic susceptibility
  • Neoplasms

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