| Acetyl-CoA carboxylase {alpha} gene and breast cancer susceptibility (2004) | |||||||||||||
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Abstract | |||||||||||||
| The identification of an interaction between BRCA1 and acetyl-CoA carboxylase α (ACCα), a key enzyme in lipid synthesis, led us to investigate the role of ACCα in breast cancer development, where it might contribute to the energy-sensing mechanisms of malignant transformation. In order to investigate if certain ACCα alleles may be high-risk breast cancer susceptibility alleles, 37 extended breast and breast/ovarian cancer families negative for BRCA1 and BRCA2 mutations were exhaustively screened for sequence variations in the entire coding sequence, intron-exon junctions, 5'UTR, 3'UTR and the promoter regions of the ACCα gene. Two possibly disease-associated ACCα variants were each identified in a single family and were not present in 137 controls. Multiple polymorphisms were detected in breast cancer families, including twelve SNPs where the frequency of the rare allele estimated in controls was >0.10. The observed lack of variation in the ACCα coding region along with the presence of extended areas of linkage disequilibrium and low haplotype diversity indicates an overall high preservation of this gene. The prevalence of the ACCα haplotypes composed of common polymorphisms was determined in 453 breast cancer cases and 469 female controls. One haplotype was found to be associated with a substantial and highly significant increase in breast cancer risk (OR = 3.10, 95% CI 1.87-5.14, P | |||||||||||||
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