Variation in genes coding for AMP-activated protein kinase (AMPK) and breast cancer risk in the European Prospective Investigation on Cancer (EPIC).
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.
Department of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. d.campa@dkfz.de
Daniele
D
Campa
Rainer
R
Claus
Lucie
L
Dostal
Angelika
A
Stein
Jenny
J
Chang-Claude
Karina
K
Meidtner
Heiner
H
Boeing
Anja
A
Olsen
Anne
A
Tjønneland
Kim
K
Overvad
Laudina
L
Rodríguez
Catalina
C
Bonet
Maria-José
MJ
Sánchez
Pilar
P
Amiano
José María
JM
Huerta
Aurelio
A
Barricarte
Kay-Tee
KT
Khaw
Nicholas
N
Wareham
Ruth C
RC
Travis
Naomi E
NE
Allen
Antonia
A
Trichopoulou
Christina
C
Bamia
Vassiliki
V
Benetou
Domenico
D
Palli
Claudia
C
Agnoli
Salvatore
S
Panico
Rosario
R
Tumino
Carlotta
C
Sacerdote
Henk
H
van Kranen
H
H
Bas Bueno-de-Mesquita
Petra H M
PH
Peeters
Carla H
CH
van Gils
Per
P
Lenner
Malin
M
Sund
Eiliv
E
Lund
Inger Torhild
IT
Gram
Sabina
S
Rinaldi
Veronique
V
Chajes
Isabelle
I
Romieu
Pierre
P
Engel
Marie Christine
MC
Boutron-Ruault
Françoise
F
Clavel-Chapelon
Afshan
A
Siddiq
Elio
E
Riboli
Federico
F
Canzian
Rudolf
R
Kaaks
D055372:AMP-Activated Protein Kinases / Q000235:genetics*; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D055372:AMP-Activated Protein Kinases