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Development and application of an estrogen related dietary pattern to predict postmenopausal breast cancer.

Principal Investigator
Name
Susan Steck
Degrees
PhD, MPH, RD, FAND
Institution
University of South Carolina, Department of Epidemiology and Biostatistics, Cancer Prevention and Control Program
Position Title
Associate Professor
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
PLCO-193
Initial CDAS Request Approval
Mar 25, 2016
Title
Development and application of an estrogen related dietary pattern to predict postmenopausal breast cancer.
Summary
Background: Over two-thirds of breast cancer cases are diagnosed in women over the age of 55 (1). Serum estrogen levels, along with other estrogen related risk factors such as hormone replacement therapy (HRT), have been associated with postmenopausal breast cancer in multiple studies, including the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (2-4). Although investigations of single dietary components have yielded conflicting results, there is emerging evidence that certain dietary patterns are related to breast cancer risk (5-8). Fung et al. developed a dietary pattern based on foods associated with estradiol and estrone sulfate, which was subsequently not associated with incident breast cancer in the Nurses’ Health Study (NHS)(9). Application of the same pattern in a Swedish cohort showed a positive association with breast cancer risk (10). We propose to identify the dietary components that are most significantly associated with 15 estrogen metabolites and develop an estrogen-related dietary index (ERDI). The ERDI will be applied to predict postmenopausal breast cancer risk. Use of the PLCO data will allow for improvement upon previous dietary patterns due to the inclusion of more estrogen metabolites in a more heterogeneous study population.
Methods: STEP 1: Dietary intakes from the baseline dietary questionnaire (DQX) will be used from the subset of women in the intervention arm of the PLCO with data on 15 serum estrogen metabolites used in the nested study conducted by Fuhrman et al.(11) (will include controls with no cancer diagnosis along with all breast cancer cases who were diagnosed 10 years or later after baseline serum samples were drawn, to avoid any pathogenesis that may affect estrogen levels). The intakes will be categorized into 37 food groups based on the United States Department of Agriculture (USDA) Food Pattern Equivalents Database (FPED). All foods consumed in a particular food group will be averaged into grams per day intakes for use in the EDI. Using the food group intakes, a reduced rank regression (RRR) analysis will identify foods that are associated with serum estrogen metabolites, and the ERDI score will be derived. STEP 2: After development of the ERDI, Cox proportional hazard modeling will be used to estimate the hazard ratios and 95% confidence intervals for incident breast cancer risk by quantiles of ERDI. All subjects in the PLCO intervention arm with baseline DQX data will be included in the longitudinal analysis. Additional modeling will be performed to examine risk of breast cancer in different strata of subtype (ER+/-, PR+/-, HER2+/-) in relation to the ERDI.
Significance: Results will contribute to the growing literature on the relationship between breast cancer and dietary patterns. Estrogen is a major risk factor for breast cancer. Thus, identifying dietary patterns specifically related to estrogen metabolites may show stronger associations with breast cancer than previous studies of more general healthy eating dietary patterns and lead to more targeted prevention strategies.
Aims

1. Derive an estrogen-related dietary index (ERDI) based on food groups associated with baseline serum estrogen metabolite levels using a reduced rank regression analysis.
2. Perform a descriptive analysis characterizing the study population by ERDI scores.
3. Investigate the association between ERDI and incident breast cancer risk using Cox proportional hazard modeling. The ERDI will be treated as both continuous variable and categorized in quantiles to examine the dose-response relationship.
4. Investigate the association between the ERDI and incident breast cancer risk using Cox proportional hazard modeling within strata of cancer subtypes. Strata-specific analyses will include ER+/-, PR+/-, and HER2+/-.

References
1. Society, A.C. (2015). Cancer Facts & Figures 2015. In. (Atlanta, American Cancer Society.
2. Key, T.J., Appleby, P.N., Reeves, G.K., Roddam, A., Dorgan, J.F., Longcope, C., Stanczyk, F.Z., Stephenson, H.E., Jr., Falk, R.T., Miller, R., et al. (2003). Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. Journal of the National Cancer Institute 95, 1218-1226.
3. Key, T.J. (2011). Endogenous oestrogens and breast cancer risk in premenopausal and postmenopausal women. Steroids 76, 812-815.
4. Samavat, H., and Kurzer, M.S. (2015). Estrogen metabolism and breast cancer. Cancer letters 356, 231-243.
5. Anand, P., Kunnumakkara, A.B., Sundaram, C., Harikumar, K.B., Tharakan, S.T., Lai, O.S., Sung, B., and Aggarwal, B.B. (2008). Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical research 25, 2097-2116.
6. Vera-Ramirez, L., Ramirez-Tortosa, M.C., Sanchez-Rovira, P., Ramirez-Tortosa, C.L., Granados-Principal, S., Lorente, J.A., and Quiles, J.L. (2013). Impact of diet on breast cancer risk: a review of experimental and observational studies. Critical reviews in food science and nutrition 53, 49-75.
7. Toledo, E., Salas-Salvado, J., Donat-Vargas, C., Buil-Cosiales, P., Estruch, R., Ros, E., Corella, D., Fito, M., Hu, F.B., Aros, F., et al. (2015). Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial: A Randomized Clinical Trial. JAMA, 1-9.
8. Fung, T.T., Hu, F.B., McCullough, M.L., Newby, P.K., Willett, W.C., and Holmes, M.D. (2006). Diet quality is associated with the risk of estrogen receptor-negative breast cancer in postmenopausal women. The Journal of nutrition 136, 466-472.
9. Fung, T.T., Schulze, M.B., Hu, F.B., Hankinson, S.E., and Holmes, M.D. (2012). A dietary pattern derived to correlate with estrogens and risk of postmenopausal breast cancer. Breast cancer research and treatment 132, 1157-1162.
10. Harris, H.R., Bergkvist, L., and Wolk, A. (2015). An estrogen-associated dietary pattern and breast cancer risk in the Swedish Mammography Cohort. International journal of cancer Journal international du cancer 137, 2149-2154.
11. Fuhrman, B.J., Schairer, C., Gail, M.H., Boyd-Morin, J., Xu, X., Sue, L.Y., Buys, S.S., Isaacs, C., Keefer, L.K., Veenstra, T.D., et al. (2012). Estrogen metabolism and risk of breast cancer in postmenopausal women. Journal of the National Cancer Institute 104, 326-339.

Collaborators

Susan Steck, University of South Carolina
Mark Guinter, University of South Carolina

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