DESCRIPTION: We propose to expand our current project by prospectively examining the associations between new dietary indexes and dietary patterns and risk of breast, colon, and prostate cancer in cohort studies of 121,700 women aged 30-55 years at baseline (1976, the Nurses' Health Study), 11,686 women aged 24-44 years at baseline (1989, Nurses' Healthy Study II), and 51,529 men aged 40-75 years at baseline (1986, Health Professionals Follow-up Study). Detailed dietary data have been collected through validated semi-quantitative food frequency questionnaires every 2-4 years in each cohort. This competing renewal has four specific aims: 1). We will construct overall, animal, and vegetable low-carbohydrate scores based on intakes of macronutrients and assess their associations with risk of breast cancer (NHS I, II only), colorectal cancer, and prostate cancer (HPFS only). We will consider tumor subtypes/locations as endpoints. 2). We will examine whether adherence to the 2005 Dietary Guidelines for Americans is associated with lower risk of breast, colorectal, and prostate cancers. In addition, we will evaluate the relationship between changes in dietary indices over time and subsequent risk of cancers. The temporal relationship between diet and cancer will be analyzed by using different lag-periods (e.g., 4-12 years). 3). Using a novel statistical approach, Reduced Rank Regression (RRR), we will develop diet patterns that represent the effect of diet on increased insulin resistance (as reflected by increased plasma levels of fasting insulin and C-peptide and decreased adiponectin concentrations), IGF-1 and IGFBP-3, and endogenous sex steroid hormones and examine the relationships between the identified patterns and risk of major cancers. 4). We will examine both pre- and post-diagnostic dietary patterns (including low-carbohydrate scores and the Healthy Eating Index) in relation to survival rates of patients with breast, colon, or prostate cancer. Specifically, we will examine death from any cause, death from the specific cancer, and cancer recurrence, taking into account different tumor stages and treatment. The large size of these cohorts, the prospective design, the repeated and detailed measurements of diet and covariates, the high follow-up rates, and the availability of biochemical measurements provide a unique opportunity to study the relationship between overall diet patterns and risk of the three major cancers and their survivals in an extremely cost-efficient manner. This competing renewal builds on exciting results from the current cycle of our grant and will extend to new cancer sites with tumor subtypes and also address dietary predictors of survival of three major cancers. PUBLIC HEALTH RELEVANCE: The traditional paradigm in epidemiology focuses on cancer risk in relation to a single or a few nutrients or foods. Our currently funded grant has addressed the limitations of traditional nutritional epidemiologic analyses by examining dietary patterns by considering how foods and nutrients are consumed in combinations. In the competing renewal, we propose to examine low carbohydrate diets and adherence to the 2005 Dietary Guidelines for Americans and risk of breast, colorectal, and prostate cancers in three large cohort studies. We will also examine the impact of these dietary patterns on cancer survival. In addition, we will use a novel statistical approach, Reduced Rank Regression (RRR), to develop diet patterns that represent the effect of diet on cancer biomarkers.