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; 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

doi:10.1038/bjc.2011.448

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 SilvaL. 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 journal › Article › peer-review

3 Scopus citations

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	https://doi.org/10.1038/bjc.2011.448
State	Published - Dec 6 2011

Keywords

Association study
Genetic susceptibility
Neoplasms

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1038/bjc.2011.448

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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., ... 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

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

@article{64106ce3eecc4d2689842459371c51fa,

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

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.",

keywords = "Association study, Genetic susceptibility, Neoplasms",

author = "Stevens, {K. N.} and M. Garcia-Closas and Z. Fredericksen and M. Kosel and Pankratz, {V. S.} and Hopper, {J. L.} and Dite, {G. S.} and C. Apicella and Southey, {M. C.} and Schmidt, {M. K.} and A. Broeks and {Van T Veer}, {L. J.} and Tollenaar, {R. A.E.M.} and Fasching, {P. A.} and Beckmann, {M. W.} and A. Hein and Ekici, {A. B.} and N. Johnson and J. Peto and {Dos Santos Silva}, I. and L. Gibson and E. Sawyer and I. Tomlinson and Kerin, {M. J.} and S. Chanock and J. Lissowska and Hunter, {D. J.} and Hoover, {R. N.} and Thomas, {G. D.} and Milne, {R. L.} and P{\'e}rez, {Ji Arias} and A. Gonz{\'a}lez-Neira and J. Ben{\'i}tez and B. Burwinkel and A. Meindl and Schmutzler, {R. K.} and Bartrar, {C. R.} and U. Hamann and Ko, {Y. D.} and T. Br{\"u}ning and J. Chang-Claude and R. Hein and S. Wang-Gohrke and T. D{\"o}rk and P. Sch{\"u}rmann and M. Bremer and P. Hillemanns and N. Bogdanova and Zalutsky, {J. V.} and Rogov, {Y. I.} and N. Antonenkova and A. Lindblom and S. Margolin and A. Mannermaa and V. Kataja and Kosma, {V. M.} and J. Hartikainen and G. Chenevix-Trench and X. Chen and P. Peterlongo and B. Bonanni and L. Bernard and S. Manoukian and X. Wang and J. Cerhan and Vachon, {C. M.} and J. Olson and Giles, {G. G.} and L. Baglietto and McLean, {C. A.} and G. Severi and John, {E. M.} and A. Miron and R. Winqvist and K. Pylk{\"a}s and A. Jukkola-Vuorinen and M. Grip and I. Andrulis and Knight, {J. A.} and G. Glendon and Mulligan, {A. M.} and A. Cox and Brock, {I. W.} and G. Elliott and Cross, {S. S.} and Pharoah, {P. P.} and Dunning, {A. M.} and Pooley, {K. A.} and Humphreys, {M. K.} and J. Wang and D. Kang and Yoo, {K. Y.} and Noh, {D. Y.} and S. Sangrajrang and V. Gabrieau and P. Brennan and J. McKay and H. Anton-Culver and A. Ziogas and Couch, {F. J.} and Easton, {D. F.}",

note = "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 {\textquoteleft}BOSOM{\textquoteright} 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{\textquoteright}s & St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}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 Tem{\'a}tica de Investigaci{\'o}n Cooperativa en C{\'a}ncer and grants from the Asociaci{\'o}n Espa{\~n}ola Contra el C{\'a}ncer and the Fondo de Investigaci{\'o}n Sanitario (PI081583 and PI081120). We thank Charo Alonso, Tais Moreno, Guillermo Pita, Primitiva Men{\'e}ndez 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",

year = "2011",

month = dec,

day = "6",

doi = "10.1038/bjc.2011.448",

language = "English (US)",

volume = "105",

pages = "1934--1939",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "12",

}

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 -

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

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