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Variation in genes coding for AMP-activated protein kinase (AMPK) and breast cancer risk in the European Prospective Investigation on Cancer (EPIC)

  • Epidemiology
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Abstract

AMP-activated protein kinase (AMPK) is an energy sensing/signalling intracellular protein which is activated by an increase in the cellular AMP:ATP ratio after ATP depletion. Once activated, AMPK inhibits fatty acid synthesis and the Akt-mTOR pathway, and activates the p53-p21 axis. All these molecular mechanisms are thought to play a key role in breast carcinogenesis. We investigated the genetic variability of four genes encoding AMPK (PRKAA1, PRKAA2, PRKAB1 and PRKAB2). Using a tagging approach and selecting SNPs we covered all the common genetic variation of these genes. We tested association of tagging SNPs in our four candidate genes with breast cancer (BC) risk in a study of 1340 BC cases and 2536 controls nested into the European Prospective Investigation into Cancer and Nutrition (EPIC). Given the relevance of AMPK on fatty acid synthesis and the importance of body fatness as a BC risk factor, we tested association of SNPs and body-mass index as well. We observed no statistically significant association between the SNPs in the PRKAs genes and BC risk and BMI after correction for multiple testing.

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Acknowledgments

Specific results of this study were obtained with financial support from the US Army Medical Research and Material Command (W81XWH-04-1-0271). The EPIC study was funded by “Europe Against Cancer” Programme of the European Commission (SANCO); Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM); German Cancer Aid; German Cancer Research Center; German Federal Ministry of Education and Research; Danish Cancer Society; Health Research Fund (FIS) of the Spanish Ministry of Health; the participating regional governments and institutions of Spain; Cancer Research UK; Medical Research Council, UK; Hellenic Ministry of Health and Social Solidarity; the Stavros Niarchos Foundation and the Hellenic Health Foundation; Italian Association for Research on Cancer; Italian National Research Council; Dutch Ministry of Public Health, Welfare and Sports (VWS), Dutch Ministry of Health, Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands); Statistics Netherlands; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Norwegian Cancer Society.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Daniele Campa, Rainer Claus, Lucie Dostal, Angelika Stein, Jenny Chang-Claude, Federico Canzian & Rudolf Kaaks

  2. Department of Epidemiology, Deutsches Institut für Ernährungsforschung, Potsdam-Rehbrücke, Germany

    Karina Meidtner & Heiner Boeing

  3. Institute of Cancer Epidemiology, The Danish Cancer Society, Copenhagen, Denmark

    Anja Olsen & Anne Tjønneland

  4. Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark

    Kim Overvad

  5. Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark

    Kim Overvad

  6. Public Health and Participation Directorate, Health and Health Care Services Council, Oveido, Asturias, Spain

    Laudina Rodríguez

  7. Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain

    Catalina Bonet

  8. Andalusian School of Public Health, Granada, Spain

    Maria-José Sánchez

  9. Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain

    Maria-José Sánchez, Pilar Amiano, José María Huerta & Aurelio Barricarte

  10. Public Health Division of Gipuzkoa, Instituto Investigación BioDonostia, IISBioDonostia, San Sebastian, Gipuzkoa, Spain

    Pilar Amiano

  11. Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain

    José María Huerta

  12. Navarre Public Health Institute, Pamplona, Spain

    Aurelio Barricarte

  13. University of Cambridge School of Clinical Medicine, Cambridge, UK

    Kay-Tee Khaw

  14. MRC Epidemiology Unit, Cambridge, UK

    Nicholas Wareham

  15. Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK

    Ruth C. Travis & Naomi E. Allen

  16. Hellenic Health Foundation, Athens, Greece

    Antonia Trichopoulou

  17. WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece

    Antonia Trichopoulou, Christina Bamia & Vassiliki Benetou

  18. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, Florence, Italy

    Domenico Palli

  19. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Claudia Agnoli

  20. Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy

    Salvatore Panico

  21. Cancer registry and Histopathology Unit, “Civile-M.P.Arezzo” Hospital, ASP 7, Ragusa, Italy

    Rosario Tumino

  22. Center for Cancer Prevention (CPO-Piemonte), Turin, Italy

    Carlotta Sacerdote

  23. Human Genetic Foundation (HuGeF), Turin, Italy

    Carlotta Sacerdote

  24. Centre for Nutrition and Health (CVG), National Institute for Public Health and the Environment, Bilthoven, Netherlands

    Henk van Kranen & H. Bas Bueno-de-Mesquita

  25. Julius Center, University Medical Center, Utrecht, The Netherlands

    Petra H. M. Peeters & Carla H. van Gils

  26. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

    Per Lenner

  27. Department of Surgery, Umeå University, Umeå, Sweden

    Malin Sund

  28. Institute of Community Medicine University of Tromsø, Tromsø, Norway

    Eiliv Lund & Inger Torhild Gram

  29. International Agency for Research on Cancer, Lyon, France

    Sabina Rinaldi, Veronique Chajes & Isabelle Romieu

  30. INSERM UMR 1018, Team 9: Nutrition, Hormones et Santé des femmes, Centre de Recherche en Epidémiologie et Santé des Populations, Hôpital Paul Brousse, Villejuif, France

    Pierre Engel, Marie Christine Boutron-Ruault & Françoise Clavel-Chapelon

  31. Imperial College, London, UK

    Afshan Siddiq & Elio Riboli

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  1. Daniele Campa
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  2. Rainer Claus
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  3. Lucie Dostal
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  33. Per Lenner
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  39. Isabelle Romieu
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  40. Pierre Engel
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  41. Marie Christine Boutron-Ruault
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  44. Elio Riboli
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  45. Federico Canzian
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  46. Rudolf Kaaks
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Corresponding author

Correspondence to Rudolf Kaaks.

Electronic supplementary material

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10549_2010_1269_MOESM1_ESM.xls

Supplementary Table 1. Main effects of 39 SNPs genotyped in the study on breast cancer risk. Columns in this table show: gene name; NCBI dbSNP rs number; the three possible genotypes; numbers of cases for each of the three genotypes; controls for each of the three genotypes; odds ratios for heterozygotes and odds ratios for homozygotes for the rare allele with 95% confidence interval (referred to the homozygotes for the common allele); associated P value; P value of the trend test. (XLS 34 kb)

10549_2010_1269_MOESM2_ESM.xls

Supplementary Table 2. Main effects of 39 SNPs genotyped in the study on BMI. Columns in this table show: gene name; NCBI dbSNP rs number; possible genotypes; numbers of subjects for each of the three genotypes; BMI mean for each of the three genotypes with 95% confidence interval; P value of the trend test. (XLS 31 kb)

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Campa, D., Claus, R., Dostal, L. et al. Variation in genes coding for AMP-activated protein kinase (AMPK) and breast cancer risk in the European Prospective Investigation on Cancer (EPIC). Breast Cancer Res Treat 127, 761–767 (2011). https://doi.org/10.1007/s10549-010-1269-1

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