Haplotype-based analysis of common variation in the acetyl-CoA carboxylase α gene and breast cancer risk: A case-control study nested within the European Prospective Investigation into Cancer and Nutrition

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-ClaudeHeiner 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

Research output: Contribution to journalArticlepeer-review

Abstract

A key fatty acid synthesis enzyme, acetyl-CoA carboxylase α. (ACC-α), 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-α 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-α 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-α common sequence variants in susceptibility to breast cancer and encourage studies of other genes involved in fatty acid synthesis.

Original languageEnglish
Pages (from-to)409-415
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume16
Issue number3
DOIs
Publication statusPublished - Mar 2007

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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