Variation in genes coding for AMP-activated protein kinase (AMPK) and breast cancer risk in the European Prospective Investigation on Cancer (EPIC)
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Daniele Campa Rainer Claus Lucie Dostal Angelika Stein Jenny Chang-Claude Karina Meidtner Heiner Boeing Anja Olsen Anne Tjønneland K
- چاپ و سال / کشور: 2010
Description
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.
Breast Cancer Res Treat (2011) 127:761–767 DOI 10.1007/s10549-010-1269-1 Received: 21 October 2010 / Accepted: 15 November 2010 / Published online: 30 November 2010 Springer Science+Business Media, LLC. 2010
