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

Daniele Campa, Rainer Claus, Lucie Dostal, Angelika Stein, Jenny Chang-Claude, Karina Meidtner, Heiner Boeing, Anja Olsen, Anne Tjønneland, Kim Overvad, Laudina Rodríguez, Catalina Bonet, Maria José Sánchez, Pilar Amiano, José María Huerta, Aurelio Barricarte, Kay Tee Khaw, Nicholas Wareham, Ruth C. Travis, Naomi E. AllenAntonia Trichopoulou, Christina Bamia, Vassiliki Benetou, Domenico Palli, Claudia Agnoli, Salvatore Panico, Rosario Tumino, Carlotta Sacerdote, Henk Van Kranen, H. Bas Bueno-De-Mesquita, Petra H M Peeters, Carla H. Van Gils, Per Lenner, Malin Sund, Eiliv Lund, Inger Torhild Gram, Sabina Rinaldi, Veronique Chajes, Isabelle Romieu, Pierre Engel, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Afshan Siddiq, Elio Riboli, Federico Canzian, Rudolf Kaaks

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)761-767
Number of pages7
JournalBreast Cancer Research and Treatment
Volume127
Issue number3
DOIs
Publication statusPublished - Jun 2011

Keywords

  • AMP-activated protein kinase
  • Body-mass index
  • Breast cancer
  • Cancer susceptibility

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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