title: Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk.
abstract: 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.
authors.affiliation: Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
authors.forename: James
authors.initials: J
authors.lastname: McKay
authors.forename: Olga
authors.initials: O
authors.lastname: Sinilnikova
authors.forename: Anika
authors.initials: A
authors.lastname: Hüsing
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Rikke Dalgaard
authors.initials: RD
authors.lastname: Hansen
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Petra Mariann
authors.initials: PM
authors.lastname: Witt
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Veronique
authors.initials: V
authors.lastname: Chajes
authors.forename: Sabine
authors.initials: S
authors.lastname: Rohrmann
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Anna
authors.initials: A
authors.lastname: Villarini
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
authors.forename: H
authors.initials: H
authors.lastname: Bas Bueno-de-Mesquita
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: Núria
authors.initials: N
authors.lastname: Sala
authors.forename: Laudina Rodriguez
authors.initials: LR
authors.lastname: Suarez
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.forename: Maria-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Per
authors.initials: P
authors.lastname: Lenner
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Kostas
authors.initials: K
authors.lastname: Tsilidis
authors.forename: Sheila
authors.initials: S
authors.lastname: Bingham
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Valentina
authors.initials: V
authors.lastname: Gallo
authors.forename: Teresa
authors.initials: T
authors.lastname: Norat
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Gilbert
authors.initials: G
authors.lastname: Lenoir
authors.forename: Sean V
authors.initials: SV
authors.lastname: Tavtigian
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
mesh_terms: 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*
chemical_list: 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