Haplotype-Based Analysis of Common Variation in theAcetyl-CoA Carboxylase αGene and Breast Cancer Risk: A Case-Control Study Nested within the European Prospective Investigation into Cancer and Nutrition
Year: 2007
Type: article
Study design: Observational Study
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: Olga M. Sinilnikova, James D. McKay, Sean V. Tavtigian, Federico Canzian, Deepika DeSilva, Carine Biessy, Stéphanie Monnier, Laure Dossus, Catherine Boillot, Lydie Gioia, David J. Hughes, Majken K. Jensen, Kim Overvad, Anne Tjonneland, Anja Olsen, Françoise Clavel-Chapelon, Véronique Chajès, Virginie Joulin, Jakob Linseisen, Jenny Chang-Claude, Heiner Boeing, Stephan Dahm, Antonia Trichopoulou, Dimitrios Trichopoulos, Maria Koliva, Kay-Tee Khaw, Sheila Bingham, Naomi E. Allen, Timothy Key, Domenico Palli, Salvatore Panico, Franco Berrino, Rosario Tumino, Paolo Vineis, H. Bas Bueno-de-Mesquita, Petra H. Peeters, Carla H. van Gils, Eiliv Lund, Guillem Pera, José Ramón Quirós, Miren Dorronsoro, Carmen Martínez García, María-José Tormo, Eva Ardanaz, Goran Hallmans, Per Lenner, Göran Berglund, Jonas Manjer, Elio Riboli, Gilbert M. Lenoir, Rudolf Kaaks
Institutions: Hospices Civils de Lyon, Centre Léon Bérard, Centre international de recherche sur le cancer, Aalborg University Hospital, Aarhus University Hospital, Danish Cancer Society, Institut Gustave Roussy, Centre National de la Recherche Scientifique, German Cancer Research Center, German Institute of Human Nutrition, National and Kapodistrian University of Athens, University of Cambridge, MRC Mitochondrial Biology Unit, Medical Research Council, Cancer Research UK, University of Oxford, Cancer Research UK Oxford Centre, Federico II University Hospital, University of Naples Federico II, Fondazione IRCCS Istituto Nazionale dei Tumori, Piedmont Reference Center for Epidemiology and Cancer Prevention, National Institute for Public Health and the Environment, University Medical Center Utrecht, UiT The Arctic University of Norway, Institut Català d'Oncologia, Andalusian School of Public Health, Instituto de Salud Pública de Navarra, Umeå University, University Hospital of Umeå, Imperial College London
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2167256290