• The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio.
• Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, Ohio.
• The Ohio State University Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute, Columbus, Ohio. fred.tabung@osumc.edu.

Prostate cancer is common in countries with affluent dietary patterns and represents a heterogeneous collection of subtypes with varying behavior. Reductionist strategies focusing on individual nutrients or foods have not clearly defined risk factors. We have developed mechanisms-based dietary patterns focusing upon inflammation and chronic insulin hypersecretion, processes that are hypothesized to impact prostate carcinogenesis. In the Prostate, Lung, Colorectal, and Ovarian cancer cohort, we calculated the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores from food frequency questionnaire data among 3,517 men and women who provided a blood sample at enrollment. We used these scores in multivariable-adjusted linear regression to validate EDIH and EDIP against relevant circulating biomarkers. In a separate sample of 49,317 men, we used multivariable-adjusted Cox regression to evaluate associations of EDIH and EDIP with prostate cancer (total and subtypes) risk. Participants consuming the most hyperinsulinemic diets (EDIH quintile 5) had significantly higher concentrations of C-peptide, insulin, c-reactive protein, TNFα-R2, and lower adiponectin, than those in quintile 1. Similarly, participants consuming the most proinflammatory diets had significantly higher concentrations of IL6, TNFα-R2, C-peptide, insulin, and lower adiponectin. Men consuming hyperinsulinemic diets were at higher total prostate cancer risk: HRquintile5vs1, 1.11; 95% confidence interval (CI), 1.01-1.23; P trend = 0.03, especially high-grade cancer: HRquintile5vs1, 1.18; 95% CI, 1.02-1.37; P trend = 0.06. The EDIP was not associated with prostate cancer risk. In summary, EDIH and EDIP predicted concentrations of known insulinemic and inflammatory biomarkers, and EDIH further predicted risk of future prostate cancer. Interventions to reduce the adverse role of hyperinsulinemic diets may be a means of prostate cancer prevention.