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 publication

DOI

10.1007/s10549-010-1269-1

Type

Journal article

Journal

Breast Cancer Res Treat

Publication Date

06/2011

Volume

127

Pages

761 - 767

Keywords

AMP-Activated Protein Kinases, Adult, Aged, Body Mass Index, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors