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

K. N. Stevens, M. Garcia-Closas, Z. Fredericksen, M. Kosel, V. S. Pankratz, J. L. Hopper, G. S. Dite, C. Apicella, M. C. Southey, M. K. Schmidt, A. Broeks, L. J. Van T Veer, R. A E M Tollenaar, P. A. Fasching, M. W. Beckmann, A. Hein, A. B. Ekici, N. Johnson, J. Peto, I. Dos Santos Silva & 81 others L. Gibson, E. Sawyer, I. Tomlinson, M. J. Kerin, S. Chanock, J. Lissowska, D. J. Hunter, R. N. Hoover, G. D. Thomas, R. L. Milne, Ji Arias Pérez, A. González-Neira, J. Benítez, B. Burwinkel, A. Meindl, R. K. Schmutzler, C. R. Bartrar, U. Hamann, Y. D. Ko, T. Brüning, J. Chang-Claude, R. Hein, S. Wang-Gohrke, T. Dörk, P. Schürmann, M. Bremer, P. Hillemanns, N. Bogdanova, J. V. Zalutsky, Y. I. Rogov, N. Antonenkova, A. Lindblom, S. Margolin, A. Mannermaa, V. Kataja, V. M. Kosma, J. Hartikainen, G. Chenevix-Trench, X. Chen, P. Peterlongo, B. Bonanni, L. Bernard, S. Manoukian, X. Wang, J. Cerhan, C. M. Vachon, J. Olson, G. G. Giles, L. Baglietto, C. A. McLean, G. Severi, E. M. John, A. Miron, R. Winqvist, K. Pylkäs, A. Jukkola-Vuorinen, M. Grip, I. Andrulis, J. A. Knight, G. Glendon, A. M. Mulligan, A. Cox, I. W. Brock, G. Elliott, S. S. Cross, P. P. Pharoah, A. M. Dunning, K. A. Pooley, M. K. Humphreys, J. Wang, D. Kang, K. Y. Yoo, D. Y. Noh, S. Sangrajrang, V. Gabrieau, P. Brennan, J. McKay, H. Anton-Culver, A. Ziogas, F. J. Couch, D. F. Easton

Research output: Contribution to journalArticle

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 (US)
Pages (from-to)1934-1939
Number of pages6
JournalBritish Journal of Cancer
Volume105
Issue number12
DOIs
StatePublished - Dec 6 2011
Externally publishedYes

Fingerprint

1-Phosphatidylinositol 4-Kinase
Oncogenes
Catalytic Domain
Breast Neoplasms
Genetic Predisposition to Disease
Genetic Markers
Odds Ratio
Confidence Intervals
Estrogen Receptors
Single Nucleotide Polymorphism
Neoplasms
Lymph Nodes
Neoplasm Metastasis
Mutation

Keywords

  • Association study
  • Genetic susceptibility
  • Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Stevens, K. N., Garcia-Closas, M., Fredericksen, Z., Kosel, M., Pankratz, V. S., Hopper, J. L., ... Easton, D. F. (2011). Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk. British Journal of Cancer, 105(12), 1934-1939. https://doi.org/10.1038/bjc.2011.448

Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk. / Stevens, K. N.; Garcia-Closas, M.; Fredericksen, Z.; Kosel, M.; Pankratz, V. S.; Hopper, J. L.; Dite, G. S.; Apicella, C.; Southey, M. C.; Schmidt, M. K.; Broeks, A.; Van T Veer, L. J.; Tollenaar, R. A E M; Fasching, P. A.; Beckmann, M. W.; Hein, A.; Ekici, A. B.; Johnson, N.; Peto, J.; Dos Santos Silva, I.; Gibson, L.; Sawyer, E.; Tomlinson, I.; Kerin, M. J.; Chanock, S.; Lissowska, J.; Hunter, D. J.; Hoover, R. N.; Thomas, G. D.; Milne, R. L.; Pérez, Ji Arias; González-Neira, A.; Benítez, J.; Burwinkel, B.; Meindl, A.; Schmutzler, R. K.; Bartrar, C. R.; Hamann, U.; Ko, Y. D.; Brüning, T.; Chang-Claude, J.; Hein, R.; Wang-Gohrke, S.; Dörk, T.; Schürmann, P.; Bremer, M.; Hillemanns, P.; Bogdanova, N.; Zalutsky, J. V.; Rogov, Y. I.; Antonenkova, N.; Lindblom, A.; Margolin, S.; Mannermaa, A.; Kataja, V.; Kosma, V. M.; Hartikainen, J.; Chenevix-Trench, G.; Chen, X.; Peterlongo, P.; Bonanni, B.; Bernard, L.; Manoukian, S.; Wang, X.; Cerhan, J.; Vachon, C. M.; Olson, J.; Giles, G. G.; Baglietto, L.; McLean, C. A.; Severi, G.; John, E. M.; Miron, A.; Winqvist, R.; Pylkäs, K.; Jukkola-Vuorinen, A.; Grip, M.; Andrulis, I.; Knight, J. A.; Glendon, G.; Mulligan, A. M.; Cox, A.; Brock, I. W.; Elliott, G.; Cross, S. S.; Pharoah, P. P.; Dunning, A. M.; Pooley, K. A.; Humphreys, M. K.; Wang, J.; Kang, D.; Yoo, K. Y.; Noh, D. Y.; Sangrajrang, S.; Gabrieau, V.; Brennan, P.; McKay, J.; Anton-Culver, H.; Ziogas, A.; Couch, F. J.; Easton, D. F.

In: British Journal of Cancer, Vol. 105, No. 12, 06.12.2011, p. 1934-1939.

Research output: Contribution to journalArticle

Stevens, KN, Garcia-Closas, M, Fredericksen, Z, Kosel, M, Pankratz, VS, Hopper, JL, Dite, GS, Apicella, C, Southey, MC, Schmidt, MK, Broeks, A, Van T Veer, LJ, Tollenaar, RAEM, Fasching, PA, Beckmann, MW, Hein, A, Ekici, AB, Johnson, N, Peto, J, Dos Santos Silva, I, Gibson, L, Sawyer, E, Tomlinson, I, Kerin, MJ, Chanock, S, Lissowska, J, Hunter, DJ, Hoover, RN, Thomas, GD, Milne, RL, Pérez, JA, González-Neira, A, Benítez, J, Burwinkel, B, Meindl, A, Schmutzler, RK, Bartrar, CR, Hamann, U, Ko, YD, Brüning, T, Chang-Claude, J, Hein, R, Wang-Gohrke, S, Dörk, T, Schürmann, P, Bremer, M, Hillemanns, P, Bogdanova, N, Zalutsky, JV, Rogov, YI, Antonenkova, N, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, J, Chenevix-Trench, G, Chen, X, Peterlongo, P, Bonanni, B, Bernard, L, Manoukian, S, Wang, X, Cerhan, J, Vachon, CM, Olson, J, Giles, GG, Baglietto, L, McLean, CA, Severi, G, John, EM, Miron, A, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, I, Knight, JA, Glendon, G, Mulligan, AM, Cox, A, Brock, IW, Elliott, G, Cross, SS, Pharoah, PP, Dunning, AM, Pooley, KA, Humphreys, MK, Wang, J, Kang, D, Yoo, KY, Noh, DY, Sangrajrang, S, Gabrieau, V, Brennan, P, McKay, J, Anton-Culver, H, Ziogas, A, Couch, FJ & Easton, DF 2011, 'Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk', British Journal of Cancer, vol. 105, no. 12, pp. 1934-1939. https://doi.org/10.1038/bjc.2011.448
Stevens KN, Garcia-Closas M, Fredericksen Z, Kosel M, Pankratz VS, Hopper JL et al. Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk. British Journal of Cancer. 2011 Dec 6;105(12):1934-1939. https://doi.org/10.1038/bjc.2011.448
Stevens, K. N. ; Garcia-Closas, M. ; Fredericksen, Z. ; Kosel, M. ; Pankratz, V. S. ; Hopper, J. L. ; Dite, G. S. ; Apicella, C. ; Southey, M. C. ; Schmidt, M. K. ; Broeks, A. ; Van T Veer, L. J. ; Tollenaar, R. A E M ; Fasching, P. A. ; Beckmann, M. W. ; Hein, A. ; Ekici, A. B. ; Johnson, N. ; Peto, J. ; Dos Santos Silva, I. ; Gibson, L. ; Sawyer, E. ; Tomlinson, I. ; Kerin, M. J. ; Chanock, S. ; Lissowska, J. ; Hunter, D. J. ; Hoover, R. N. ; Thomas, G. D. ; Milne, R. L. ; Pérez, Ji Arias ; González-Neira, A. ; Benítez, J. ; Burwinkel, B. ; Meindl, A. ; Schmutzler, R. K. ; Bartrar, C. R. ; Hamann, U. ; Ko, Y. D. ; Brüning, T. ; Chang-Claude, J. ; Hein, R. ; Wang-Gohrke, S. ; Dörk, T. ; Schürmann, P. ; Bremer, M. ; Hillemanns, P. ; Bogdanova, N. ; Zalutsky, J. V. ; Rogov, Y. I. ; Antonenkova, N. ; Lindblom, A. ; Margolin, S. ; Mannermaa, A. ; Kataja, V. ; Kosma, V. M. ; Hartikainen, J. ; Chenevix-Trench, G. ; Chen, X. ; Peterlongo, P. ; Bonanni, B. ; Bernard, L. ; Manoukian, S. ; Wang, X. ; Cerhan, J. ; Vachon, C. M. ; Olson, J. ; Giles, G. G. ; Baglietto, L. ; McLean, C. A. ; Severi, G. ; John, E. M. ; Miron, A. ; Winqvist, R. ; Pylkäs, K. ; Jukkola-Vuorinen, A. ; Grip, M. ; Andrulis, I. ; Knight, J. A. ; Glendon, G. ; Mulligan, A. M. ; Cox, A. ; Brock, I. W. ; Elliott, G. ; Cross, S. S. ; Pharoah, P. P. ; Dunning, A. M. ; Pooley, K. A. ; Humphreys, M. K. ; Wang, J. ; Kang, D. ; Yoo, K. Y. ; Noh, D. Y. ; Sangrajrang, S. ; Gabrieau, V. ; Brennan, P. ; McKay, J. ; Anton-Culver, H. ; Ziogas, A. ; Couch, F. J. ; Easton, D. F. / Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk. In: British Journal of Cancer. 2011 ; Vol. 105, No. 12. pp. 1934-1939.
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keywords = "Association study, Genetic susceptibility, Neoplasms",
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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.

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

VL - 105

SP - 1934

EP - 1939

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 12

ER -