TY - JOUR
T1 - Haplotype-based analysis of common variation in the acetyl-CoA carboxylase α gene and breast cancer risk
T2 - A case-control study nested within the European Prospective Investigation into Cancer and Nutrition
AU - Sinilnikova, Olga M.
AU - McKay, James D.
AU - Tavtigian, Sean V.
AU - Canzian, Federico
AU - DeSilva, Deepika
AU - Biessy, Carine
AU - Monnier, Stéphanie
AU - Dossus, Laure
AU - Boillot, Catherine
AU - Gioia, Lydie
AU - Hughes, David J.
AU - Jensen, Majken K.
AU - Overvad, Kim
AU - Tjonneland, Anne
AU - Olsen, Anja
AU - Clavel-Chapelon, Françoise
AU - Chajès, Véronique
AU - Joulin, Virginie
AU - Linseisen, Jakob
AU - Chang-Claude, Jenny
AU - Boeing, Heiner
AU - Dahm, Stephan
AU - Trichopoulou, Antonia
AU - Trichopoulos, Dimitrios
AU - Koliva, Maria
AU - Khaw, Kay Tee
AU - Bingham, Sheila
AU - Allen, Naomi E.
AU - Key, Timothy
AU - Palli, Domenico
AU - Panico, Salvatore
AU - Berrino, Franco
AU - Tumino, Rosario
AU - Vineis, Paolo
AU - Bueno-de-Mesquita, H. Bas
AU - Peeters, Petra H.
AU - Van Gils, Carla H.
AU - Lund, Eiliv
AU - Pera, Guillem
AU - Quirós, José Ramón
AU - Dorronsoro, Miren
AU - García, Carmen Martínez
AU - Tormo, María José
AU - Ardanaz, Eva
AU - Hallmans, Goran
AU - Lenner, Per
AU - Berglund, Göran
AU - Manjer, Jonas
AU - Riboli, Elio
AU - Lenoir, Gilbert M.
AU - Kaaks, Rudolf
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=34047273734&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-06-0617
DO - 10.1158/1055-9965.EPI-06-0617
M3 - Article
C2 - 17372234
AN - SCOPUS:34047273734
VL - 16
SP - 409
EP - 415
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
SN - 1055-9965
IS - 3
ER -