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Haplotype-based analysis of common variation in the acetyl-CoA carboxyiase alpha gene and breast cancer risk: A case-control study nested within the European prospective investigation into cancer and nutrition

Sinilnikova, Olga M.; McKay, James D.; Tavtigian, Sean V.; Canzian, Federico; DeSilva, Deepika; Biessy, Carine; Monnier, Stephanie; Dossus, Laure; Boillot, Catherine and Gioia, Lydie, et al. (2007) In Cancer Epidemiology Biomarkers & Prevention 16(3). p.409-415
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 haplotypetagging polymorphisms efficiently capturing common variation within 325 kb of ACC-alpha and surrounding sequences using genotype data from the HapMap... (More)
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 haplotypetagging 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. (Less)
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Cancer Epidemiology Biomarkers & Prevention
volume
16
issue
3
pages
409 - 415
publisher
American Association for Cancer Research
external identifiers
  • wos:000245093900012
  • scopus:34047273734
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-06-0617
language
English
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1b16a995-f901-4e8b-a428-207da98519e1 (old id 669883)
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2007-12-14 15:47:45
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@article{1b16a995-f901-4e8b-a428-207da98519e1,
  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 haplotypetagging 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.},
  author       = {Sinilnikova, Olga M. and McKay, James D. and Tavtigian, Sean V. and Canzian, Federico and DeSilva, Deepika and Biessy, Carine and Monnier, Stephanie and Dossus, Laure and Boillot, Catherine and Gioia, Lydie and Hughes, David J. and Jensen, Majken K. and Overvad, Kim and Tjonneland, Anne and Olsen, Anja and Clavel-Chapelon, Francoise and Chajes, Veronique and Joulin, Virginie and Linseisen, Jakob and Chang-Claude, Jenny and Boeing, Heiner and Dahm, Stephan and Trichopoulou, Antonia and Trichopoulos, Dimitrios and Koliva, Maria and Khaw, Kay-Tee and Bingham, Sheila and Allen, Naomi E. and Key, Timothy and Palli, Domenico and Panico, Salvatore and Berrino, Franco and Tumino, Rosario and Vineis, Paolo and Bueno-de-Mesquita, H. Bas and Peeters, Petra H. and van Gils, Carla H. and Lund, Eiliv and Pera, Guillem and Quiros, Jose Ramon and Dorronsoro, Miren and Martinez Garcia, Carmen and Tormo, Maria-Jose and Ardanaz, Eva and Hallmans, Goran and Lenner, Per and Berglund, Goran and Manjer, Jonas and Riboli, Elio and Lenoir, Gilbert M. and Kaaks, Rudolf},
  issn         = {1538-7755},
  language     = {eng},
  number       = {3},
  pages        = {409--415},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Haplotype-based analysis of common variation in the acetyl-CoA carboxyiase alpha gene and breast cancer risk: A case-control study nested within the European prospective investigation into cancer and nutrition},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-06-0617},
  volume       = {16},
  year         = {2007},
}