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 language | English (US) |
---|---|
Pages (from-to) | 1934-1939 |
Number of pages | 6 |
Journal | British journal of cancer |
Volume | 105 |
Issue number | 12 |
DOIs | |
State | Published - Dec 6 2011 |
Keywords
- Association study
- Genetic susceptibility
- Neoplasms
ASJC Scopus subject areas
- Oncology
- Cancer Research
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Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk. / Stevens, K. N.; Garcia-Closas, M.; Fredericksen, Z. et al.
In: British journal of cancer, Vol. 105, No. 12, 06.12.2011, p. 1934-1939.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk
AU - Stevens, K. N.
AU - Garcia-Closas, M.
AU - Fredericksen, Z.
AU - Kosel, M.
AU - Pankratz, V. S.
AU - Hopper, J. L.
AU - Dite, G. S.
AU - Apicella, C.
AU - Southey, M. C.
AU - Schmidt, M. K.
AU - Broeks, A.
AU - Van T Veer, L. J.
AU - Tollenaar, R. A.E.M.
AU - Fasching, P. A.
AU - Beckmann, M. W.
AU - Hein, A.
AU - Ekici, A. B.
AU - Johnson, N.
AU - Peto, J.
AU - Dos Santos Silva, I.
AU - Gibson, L.
AU - Sawyer, E.
AU - Tomlinson, I.
AU - Kerin, M. J.
AU - Chanock, S.
AU - Lissowska, J.
AU - Hunter, D. J.
AU - Hoover, R. N.
AU - Thomas, G. D.
AU - Milne, R. L.
AU - Pérez, Ji Arias
AU - González-Neira, A.
AU - Benítez, J.
AU - Burwinkel, B.
AU - Meindl, A.
AU - Schmutzler, R. K.
AU - Bartrar, C. R.
AU - Hamann, U.
AU - Ko, Y. D.
AU - Brüning, T.
AU - Chang-Claude, J.
AU - Hein, R.
AU - Wang-Gohrke, S.
AU - Dörk, T.
AU - Schürmann, P.
AU - Bremer, M.
AU - Hillemanns, P.
AU - Bogdanova, N.
AU - Zalutsky, J. V.
AU - Rogov, Y. I.
AU - Antonenkova, N.
AU - Lindblom, A.
AU - Margolin, S.
AU - Mannermaa, A.
AU - Kataja, V.
AU - Kosma, V. M.
AU - Hartikainen, J.
AU - Chenevix-Trench, G.
AU - Chen, X.
AU - Peterlongo, P.
AU - Bonanni, B.
AU - Bernard, L.
AU - Manoukian, S.
AU - Wang, X.
AU - Cerhan, J.
AU - Vachon, C. M.
AU - Olson, J.
AU - Giles, G. G.
AU - Baglietto, L.
AU - McLean, C. A.
AU - Severi, G.
AU - John, E. M.
AU - Miron, A.
AU - Winqvist, R.
AU - Pylkäs, K.
AU - Jukkola-Vuorinen, A.
AU - Grip, M.
AU - Andrulis, I.
AU - Knight, J. A.
AU - Glendon, G.
AU - Mulligan, A. M.
AU - Cox, A.
AU - Brock, I. W.
AU - Elliott, G.
AU - Cross, S. S.
AU - Pharoah, P. P.
AU - Dunning, A. M.
AU - Pooley, K. A.
AU - Humphreys, M. K.
AU - Wang, J.
AU - Kang, D.
AU - Yoo, K. Y.
AU - Noh, D. Y.
AU - Sangrajrang, S.
AU - Gabrieau, V.
AU - Brennan, P.
AU - McKay, J.
AU - Anton-Culver, H.
AU - Ziogas, A.
AU - Couch, F. J.
AU - Easton, D. F.
N1 - Funding Information: the German Social Accident Insurance (IPA), Bochum, Germany (TB, Beate Pesch, Volker Harth, Sylvia Rabstein). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Kran-kenhaus, Bonn, Germany. kConFab Investigators, Australian Ovarian Cancer Study Group Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne VIC 3002, Australia. Funding Information: The ABCS study was funded by the Dutch Cancer Society (grants NKI 2001-2423; NKI 2007-3839), the Dutch National Genomics Initiative; ABCS acknowledges all patients, and Sten Cornelissen, Richard van Hien, Flora van Leeuwen, Vincent Smit and other contributors to the ‘BOSOM’ study (ABCS). The ABCFS, NC-BCFR and OFBCR works were supported by the United States National Cancer Institute, National Institutes of Health (NIH) under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638). Samples from the NC-BCFR were processed and distributed by the Coriell Institute for Medical Research. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products or organisations imply endorsement by the US Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. JLH is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. MCS is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. BBCC is funded in part by the ELAN fund of the University Hospital Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre. The CNIO-BCS was supported by the Genome Spain Foundation, the Red Temática de Investigación Cooperativa en Cáncer and grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario (PI081583 and PI081120). We thank Charo Alonso, Tais Moreno, Guillermo Pita, Primitiva Menéndez and Pilar Zamora for their contribution to this work. The GC-HBOC was collected within a project funded by the Deutsche Krebshilfe (Grant number: 107054). It was supported by the Dietmar-Hopp Foundation, the Helmholtz society and the German Cancer Research Center (DKFZ). We thank Sandrine Tchatchou for genotyping. The HABCS was supported by an intramural grant from Hannover Medical School. The HMBCS was supported by short-term fellowships from the German Academic Exchange Program (to NB), and the Friends of Hannover Medical School (to NB). KARBAC acknowledges The Swedish Cancer Society and The Stockholm Cancer Society. KBCP is supported by grants from the Finnish Cancer Society; the Academy of Finland (grant number 127220); the special Government Funding (EVO) of Kuopio University Hospital (grant number 5654113 and 5501) and by
PY - 2011/12/6
Y1 - 2011/12/6
N2 - 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.
AB - 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.
KW - Association study
KW - Genetic susceptibility
KW - Neoplasms
UR - http://www.scopus.com/inward/record.url?scp=84856024444&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856024444&partnerID=8YFLogxK
U2 - 10.1038/bjc.2011.448
DO - 10.1038/bjc.2011.448
M3 - Article
C2 - 22033276
AN - SCOPUS:84856024444
VL - 105
SP - 1934
EP - 1939
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 12
ER -