Fatty Acid Synthesis Gene Variants and Breast Cancer Risk: A Study within the European Prospective Investigation into Cancer and Nutrition

摘要

A western lifestyle, characterized by low rates of energy expenditure and a high-energy diet rich in saturated fats and refined carbohydrates, is associated with high incidence of breast cancer in women. Excess energy intake causes elevated blood levels of glucose and insulin, factors hat induce fatty acid synthesis and are implicated in the etiology of breast cancer. We recently discovered a highly specific interaction between ACCalpha and the protein coded by the breast cancer susceptibility gene BRCA1, which further supports a possible central role of lipogenic enzymes in breast cancer development. The above data led us to hypothesize that certain alleles of genes involved in cellular fatty acid synthesis confer increased breast cancer susceptibility. In a series of 46 breast cancer cases, we are systematically searching the coding and regulatory regions of seven selected candidate genes for polymorphic variations. Using a large case-control study nested within the EPIC cohort, we will examine associations of these sequence variants, and their haplotypes, with breast cancer risk. The key research accomplishments of the first year of the award are identification of sequency variations and assessment of haplotypes of the ACCalpha, AMPKalpha1, AMPKalpha2 and ChREBP genes coding for key lipogenic enzymes and their principal regulatory factors to be examined for association with breast cancer risk.