Investigating the Association between Iron and Breast Cancer Risk and Factors Associated with Iron Status among Canadian Women

Iron is an essential nutrient but also a potent contributor to oxidative stress. Changes in iron status across reproductive stages may have important implications for women’s health. This dissertation investigates the role of iron as a potential risk factor for breast cancer and assesses determinants of body iron status among Canadian women. First, a systematic review and meta-analysis was conducted to evaluate associations between iron and breast cancer risk. When comparing the highest vs. lowest category, heme iron intake and serum iron, but not other measures of iron intake or body iron status, were positively associated with breast cancer risk, with pooled relative risks of 1.12 (95% CI: 1.04–1.22) and 1.22 (95% CI: 1.01–1.47), respectively. Nonlinear dose-response was also observed. Second, in a population-based case-control study of Ontario women (3030 cases, 3402 controls), iron intake was not associated with overall breast cancer risk. Among premenopausal women, higher intakes of total, dietary, and dietary nonheme iron were associated with increased risk of hormone receptor-negative breast cancer. Among postmenopausal women, heme iron and supplemental iron were positively and inversely associated with breast cancer risk, respectively. Among women providing DNA (1696 cases, 1761 controls), those with genotypes resulting in reduced antioxidant capacity, particularly glutathione S-transferase deletions, were most susceptible to the effects of higher dietary iron intake. Third, based on nationally representative data from the Canadian Health Measures Survey, iron deficiency affects 16% and 4% of pre- and postmenopausal women, respectively, whereas 21% of postmenopausal women have elevated iron stores as defined by serum ferritin levels. Age, East/Southeast Asian (vs. White) race/ethnicity, alcohol consumption, and red meat (main source of heme iron) consumption were positively associated with serum ferritin in both pre- and postmenopausal women; aspirin use and dairy consumption were inversely associated with serum ferritin in postmenopausal women. Overall, these results suggest that heme iron may be a major contributor to body iron stores and a potential risk factor for breast cancer, especially among postmenopausal women. This dissertation provides additional insights into iron’s role in breast cancer etiology and highlights the importance of considering elevated iron stores in addition to iron deficiency.Ph.D