Journal article

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

KN Stevens, M Garcia-Closas, Z Fredericksen, M Kosel, VS Pankratz, JL Hopper, GS Dite, C Apicella, MC Southey, MK Schmidt, A Broeks, LJ Van 't Veer, RAEM Tollenaar, PA Fasching, MW Beckmann, A Hein, AB Ekici, N Johnson, J Peto, I dos Santos Silva Show all



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 (..

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Awarded by Dutch Cancer Society

Awarded by United States National Cancer Institute, National Institutes of Health (NIH)

Awarded by Fondo de Investigacion Sanitario

Awarded by Deutsche Krebshilfe

Awarded by Academy of Finland

Awarded by Kuopio University Hospital

Awarded by National Breast Cancer Foundation and Cancer Australia

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by United States Army Medical Research and Materiel Command

Awarded by NIH

Awarded by US Recovery act

Awarded by National Institutes of Health, National Cancer Institute

Awarded by Lon V Smith Foundation


Awarded by Cancer Research UK

Awarded by National Institute for Health Research

Funding Acknowledgements

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 Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI081583 and PI081120). We thank Charo Alonso, Tais Moreno, Guillermo Pita, Primitiva Menendez 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 the strategic funding of the University of Eastern Finland. We thank Mrs Helena Kemilainen, Mrs Aija Parkkinen and Mrs Eija Myohanen for their skillful technical assistance.We thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded 2001-2009 by NHMRC and currently by theNational Breast Cancer Foundation and Cancer Australia #628333) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17-01-1-0729); the Cancer Council of Tasmania and Cancer Foundation of Western Australia; and the NHMRC [199600]. GC-T is supported by the NHMRC. PP is supported by funds from Italian citizens who allocated the 5 x 1000 share of their tax payment to the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5 x 1000'). MBCSG thanks Paolo Radice, Bernard Peissel, Daniela Zaffaroni and Marco A Pierotti of the Fondazione IRCCS Istituto Nazionale Tumori and Monica Barile of the Istituto Europeo di Oncologia, Milano, Italy. MCBCS was supported by NIH grant CA122340 and US Recovery act award CA122340Z. Many people have contributed to the MCCS, including the original investigators and the diligent teams who recruited the participants and who continue working on follow-up. Finally, we express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. Cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Oulu and the Oulu University Hospital. SBCS was funded by the Breast Cancer Campaign and Yorkshire Cancer Research. The authors acknowledge Helen Cramp, Sue Higham, Dan Connley, Saba Balasubramanian. The UCIBCS is supported by the National Institutes of Health, National Cancer Institute grants CA-58860, CA-92044 and the Lon V Smith Foundation grant LVS-39420.