Author: Joanne KotsopoulosPublisher:
ISBN: 9780494280560
Category :
Languages : en
Pages : 554
Book Description
The lifetime risk of developing breast cancer due to an inherited mutation in the breast cancer susceptibility gene, BRCA1, is estimated to be 80%. Management options include screening for early detection or primary prevention with prophylactic surgery or drug therapy. The limited uptake of these options illustrates the need to explore alternative preventive strategies that include dietary or lifestyle changes. Prospective trials using breast cancer as the principle endpoint when evaluating the protective role of nutrients is not feasible in this high-risk population. BRCA1 helps maintain genomic integrity through the participation in antioxidant responses and the repair of double-stranded DNA breaks. Thus, the overall goal of this dissertation was to exploit the known functions of the BRCA1 protein to elucidate a biomarker that could distinguish between BRCA1 mutation carriers and non-carriers, and furthermore, to correlate these markers of susceptibility with levels of dietary factors, more specifically, coffee, selenium and lycopene. These nutrients were selected based on the hypothesis that dietary changes that decrease oxidative damage (possibly linked to estrogen exposure) or enhance the DNA damage repair pathways, may modulate breast cancer risk. We evaluated the ability of a panel of biomarkers that reflected both DNA repair capacity and oxidative status to predict the presence of a BRCA1 mutation, and found no difference. Coffee consumption was associated with a significant reduction in breast cancer risk among mutation carriers. Among women with a BRCA1 mutation, toenail selenium was associated with significantly lower levels of chromosomal damage as assessed by the micronucleus test. An increase in oxidative damage to proteins, and to a lesser extent, lipids, with increasing dietary lycopene intake was limited to mutation carriers. These pro-oxidant effects require confirmation. Collectively, these findings translate into the prevention of BRCA1-associated breast cancer through interventions with selenium and other factors that may minimize chromosomal damage. The prospect of unique diets to prevent hereditary breast cancer may therefore be possible by protecting genomic stability due to an inherited BRCA1 mutation.
