Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk.
Fatty acid synthase (FAS) is the major enzyme of lipogenesis. It catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to produce palmitic acid. Transcription of the FAS gene is controlled synergistically by the transcription factors ChREBP (carbohydrate response element-binding protein), which is induced by glucose, and SREBP-1 (sterol response element-binding protein-1), which is stimulated by insulin through the PI3K/Akt signal transduction pathway. We investigated whether the genetic variability of the genes encoding for ChREBP, SREBP and FAS (respectively, MLXIPL, SREBF1 and FASN) is related to breast cancer risk and body-mass index (BMI) by studying 1,294 breast cancer cases and 2,452 controls from the European Prospective Investigation on Cancer (EPIC). We resequenced the FAS gene and combined information of SNPs found by resequencing and SNPs from public databases. Using a tagging approach and selecting 20 SNPs, we covered all the common genetic variation of these genes. In this study we were not able to find any statistically significant association between the SNPs in the FAS, ChREBP and SREPB-1 genes and an increased risk of breast cancer overall and by subgroups of age, menopausal status, hormone replacement therapy (HRT) use or BMI. On the other hand, we found that two SNPs in FASN were associated with BMI.
Campa
Daniele
D
Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
McKay
James
J
Sinilnikova
Olga
O
Hüsing
Anika
A
Vogel
Ulla
U
Hansen
Rikke Dalgaard
RD
Overvad
Kim
K
Witt
Petra Mariann
PM
Clavel-Chapelon
Françoise
F
Boutron-Ruault
Marie-Christine
MC
Chajes
Veronique
V
Rohrmann
Sabine
S
Chang-Claude
Jenny
J
Boeing
Heiner
H
Fisher
Eva
E
Trichopoulou
Antonia
A
Trichopoulos
Dimitrios
D
Palli
Domenico
D
Villarini
Anna
A
Sacerdote
Carlotta
C
Mattiello
Amalia
A
Tumino
Rosario
R
Peeters
Petra H M
PH
van Gils
Carla H
CH
Bas Bueno-de-Mesquita
H
H
Lund
Eiliv
E
Chirlaque
María Dolores
MD
Sala
Núria
N
Suarez
Laudina Rodriguez
LR
Barricarte
Aurelio
A
Dorronsoro
Miren
M
Sánchez
Maria-José
MJ
Lenner
Per
P
Hallmans
Göran
G
Tsilidis
Kostas
K
Bingham
Sheila
S
Khaw
Kay-Tee
KT
Gallo
Valentina
V
Norat
Teresa
T
Riboli
Elio
E
Rinaldi
Sabina
S
Lenoir
Gilbert
G
Tavtigian
Sean V
SV
Canzian
Federico
F
Kaaks
Rudolf
R
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000235:genetics*; D054890:Fatty Acid Synthase, Type I / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D009765:Obesity / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C116385:MLXIPL protein, human; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I