Abstract: Background: The etiology of prostate cancer (PCa) is not well-known, and the role of diet is not well established. We aimed to evaluate the role of the inflammatory power of the diet, measured by the Dietary Inflammatory Index (DII®), on the risk of PCa. Methodology: A population-based multicase-control (MCC-Spain) study was conducted. Information was collected on sociodemographic characteristics, personal and family antecedents, and lifestyles, including diet from a Food Frequency Questionnaire. The inflammatory potential of the diet was assessed using the energy-adjusted Dietary Inflammatory Index (E-DII) based on 30 parameters (a higher score indicates a higher inflammatory capacity of the diet). Tertiles of E-DII were created using the cut-off points from the control group. The International Society of Urology Pathology (ISUP) was grouped as ISUP 1, ISUP 2, or ISUP 3-5. Unconditional logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association between E-DII score and PCa risk. Results: A total of 928 PCa cases and 1278 population controls were included. Among PCa cases, the mean value of the E-DII score was 0.18 (SD: 1.9) vs. 0.07 (SD: 1.9) in the control group (p = 0.162). Cases with a more pro-inflammatory diet (3rd tertile) had the highest risk of PCa, aORT3vsT1 = 1.30 (95% CI 1.03-1.65) (p-trend = 0.026). When stratifying by ISUP, this risk association was observed only for ISUP 2 and ISUP 3-5, aORT3vsT1 = 1.46 (95% CI 1.02-2.10) and 1.60 (95% CI 1.10-2.34), respectively. Conclusion: A positive association was observed between consuming a pro-inflammatory diet and PCa in the MCC-Spain population, specifically for an ISUP grade greater or equal than 2.

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