Dietary and Reproductive Risk Factors for Breast Cancer in the Nurses' Health Studies
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CitationSisti, Julia Shafto. 2015. Dietary and Reproductive Risk Factors for Breast Cancer in the Nurses' Health Studies. Doctoral dissertation, Harvard T.H. Chan School of Public Health.
AbstractBreast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among US women. Several hormonal, anthropometric, lifestyle, and genetic factors are known to be associated with breast cancer, though these associations may differ by menopausal status and molecular subtype. Studying risk factors in relation to these subtypes can help enhance our understanding of breast cancer etiology. Here, we aim to further explore the mechanisms through which several established and suspected risk factors may influence risk of breast cancer, with an emphasis on modifiable exposures, which may have direct implications for prevention strategies, particularly for premenopausal and non-luminal breast cancers.
In Chapter 1, we evaluated the cross-sectional relationship between intakes of caffeine, coffee, decaffeinated coffee, and tea, and comprehensive profiles of urinary estrogens and estrogen metabolites in premenopausal women. We found significant associations between coffee intake and metabolites in the 2-hydroxylation pathway, suggesting a possible mechanism through which coffee may affect breast cancer risk. In Chapter 2, we examined associations between premenopausal plasma carotenoid levels and markers of oxidative stress and subsequent breast cancer risk. In contrast to previously published analyses, which largely focused on postmenopausal carotenoid exposure, we did not find significant inverse associations between circulating carotenoids and risk; additionally we did not observe positive associations between fluorescent oxidation products and risk. However, we did find some evidence that the effects of carotenoids on risk may be modified by single nucleotide polymorphisms in genes related to carotenoid availability and oxidative/antioxidative processes. In Chapter 3, we explored whether the associations of reproductive risk factors with breast cancer vary by intrinsic molecular subtype. We observed evidence that many risk factors are most strongly associated with the hormone receptor-positive luminal A subtype, which comprises the majority of breast cancers, though tests of heterogeneity did not reach significance in many cases. Consistent with previous studies, we observed that breastfeeding may reduce risk of basal-like tumors, and may represent a potential preventive strategy for this aggressive subtype. In conclusion, these analyses, while varied in scope, help elucidate mechanisms by which risk factors may influence breast cancer risk.
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