title: Haplotype-based analysis of common variation in the acetyl-coA carboxylase alpha gene and breast cancer risk: a case-control study nested within the European Prospective Investigation into Cancer and Nutrition.
abstract: A key fatty acid synthesis enzyme, acetyl-CoA carboxylase alpha (ACC-alpha), has been shown to be highly expressed in human breast cancer and other tumor types and also to specifically interact with the protein coded by one of two major breast cancer susceptibility genes BRCA1. We used a comprehensive haplotype analysis to examine the contribution of the ACC-alpha common genetic variation (allele frequency >5%) to breast cancer in a case-control study (1,588 cases/2,600 controls) nested within the European Prospective Investigation into Cancer and Nutrition. We identified 21 haplotype-tagging polymorphisms efficiently capturing common variation within 325 kb of ACC-alpha and surrounding sequences using genotype data from the HapMap project and our resequencing data. We found an effect on overall risk of breast cancer in homozygous carriers of one common haplotype [odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.03-2.94]. When the data were subdivided by menopausal status, we found statistical evidence of heterogeneity for two other common haplotypes (P value for heterogeneity = 0.016 and 0.045). In premenopausal women, the carriers of these haplotypes, compared with noncarriers, had an altered risk of breast cancer (OR, 0.70; 95% CI, 0.53-0.92 and OR, 1.35; 95% CI, 1.04-1.76). These findings were not significant after adjustment for multiple testing and therefore should be considered as preliminary and evaluated in larger independent studies. However, they suggest a possible role of the ACC-alpha common sequence variants in susceptibility to breast cancer and encourage studies of other genes involved in fatty acid synthesis.
authors: IARC, Lyon, France.
authors: Olga M
authors: OM
authors: Sinilnikova
authors: James D
authors: JD
authors: McKay
authors: Sean V
authors: SV
authors: Tavtigian
authors: Federico
authors: F
authors: Canzian
authors: Deepika
authors: D
authors: DeSilva
authors: Carine
authors: C
authors: Biessy
authors: Stéphanie
authors: S
authors: Monnier
authors: Laure
authors: L
authors: Dossus
authors: Catherine
authors: C
authors: Boillot
authors: Lydie
authors: L
authors: Gioia
authors: David J
authors: DJ
authors: Hughes
authors: Majken K
authors: MK
authors: Jensen
authors: Kim
authors: K
authors: Overvad
authors: Anne
authors: A
authors: Tjonneland
authors: Anja
authors: A
authors: Olsen
authors: Françoise
authors: F
authors: Clavel-Chapelon
authors: Véronique
authors: V
authors: Chajès
authors: Virginie
authors: V
authors: Joulin
authors: Jakob
authors: J
authors: Linseisen
authors: Jenny
authors: J
authors: Chang-Claude
authors: Heiner
authors: H
authors: Boeing
authors: Stephan
authors: S
authors: Dahm
authors: Antonia
authors: A
authors: Trichopoulou
authors: Dimitrios
authors: D
authors: Trichopoulos
authors: Maria
authors: M
authors: Koliva
authors: Kay-Tee
authors: KT
authors: Khaw
authors: Sheila
authors: S
authors: Bingham
authors: Naomi E
authors: NE
authors: Allen
authors: Timothy
authors: T
authors: Key
authors: Domenico
authors: D
authors: Palli
authors: Salvatore
authors: S
authors: Panico
authors: Franco
authors: F
authors: Berrino
authors: Rosario
authors: R
authors: Tumino
authors: Paolo
authors: P
authors: Vineis
authors: H Bas
authors: HB
authors: Bueno-de-Mesquita
authors: Petra H
authors: PH
authors: Peeters
authors: Carla H
authors: CH
authors: van Gils
authors: Eiliv
authors: E
authors: Lund
authors: Guillem
authors: G
authors: Pera
authors: José Ramón
authors: JR
authors: Quirós
authors: Miren
authors: M
authors: Dorronsoro
authors: Carmen
authors: C
authors: Martínez García
authors: María-José
authors: MJ
authors: Tormo
authors: Eva
authors: E
authors: Ardanaz
authors: Goran
authors: G
authors: Hallmans
authors: Per
authors: P
authors: Lenner
authors: Göran
authors: G
authors: Berglund
authors: Jonas
authors: J
authors: Manjer
authors: Elio
authors: E
authors: Riboli
authors: Gilbert M
authors: GM
authors: Lenoir
authors: Rudolf
authors: R
authors: Kaaks
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D000103:Acetyl-CoA Carboxylase