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Abstract
The relative importance of biochemical pathways has not been previously examined when considering the influence of diet on breast cancer risk. To address this issue, we used interview data from a population-based sample of 1463 breast cancer cases and 1500 controls. Dietary intake was assessed shortly after diagnosis using a 101-item food frequency questionnaire. Age- and energy-adjusted odds ratios (ORs) for individual micro- and macronutrients were estimated with logistic regression. Hierarchical modeling was used to account for biologically plausible nutrient pathways (1-carbon metabolism, oxidative stress, glycemic control, and phytoestrogens). Effect estimates from hierarchical modeling were more precise and plausible compared to those from multivariable models. The strongest relationship observed was for the glycemic control pathway, but confidence intervals (CI) were wide [OR (95% CI): 0.86 (0.62, 1.21)]. Little or no effect was observed for the 1-carbon metabolism, oxidative stress, and phytoestrogen pathways. Associations were similar when stratified by supplement use. Our approach that emphasizes biochemical pathways, rather than individual nutrients, revealed that breast cancer risk may be more strongly associated with glycemic control factors than those from other pathways considered. Our study emphasizes the importance of accounting for multiple nutrient pathways when examining associations between dietary intake and breast cancer.
ACKNOWLEDGMENTS
This work was supported by grants from the National Cancer Institute (R01CA109753 and 3R01CA109753–04S1) and in part by grants from Department of Defense (BC031746 and W81XWH-06–1-0298) and National Cancer Institute and National Institutes of Environmental Health and Sciences (UO1CA/ES66572, UO1CA66572, P30CA013696, P30ES009089, and P30ES10126) and the Marilyn Gentry Fellowship from the American Institute for Cancer Research. The authors declare no financial or nonfinancial conflicts.
The authors would like to thank Drs. John Witte, Charles Poole, David Richardson, and Stephen Cole for their thoughtful comments on an earlier version of this work.
Patrick T. Bradshaw and Nikhil K. Khankari are joint first authors and contributed equally in the preparation of this article.