Dietary spermidine intake is not associated with prostate cancer incidence or prostate cancer-specific mortality: findings from the prostate, lung, colorectal, and ovarian cancer screening trial.

BACKGROUND: The role of dietary spermidine in prostate cancer outcomes remains unclear. We examined associations between spermidine intake and prostate cancer incidence, all-cause mortality, and prostate cancer-specific mortality in a large prospective cohort. METHODS: This study included 54,517 male participants from the PLCO cancer screening trial. Spermidine in the diet was assessed through a food frequency questionnaire. Incidence was assessed using logistic regression, all-cause mortality using Cox proportional hazards models, and prostate cancer-specific mortality using Fine-Gray competing risk models. Multivariable models adjusted for available demographic, lifestyle, and clinical covariates; total energy intake was not included because it could not be reliably calculated from the processed analytic dataset. RESULTS: During the follow-up period, a total of 6,643 cases of prostate cancer and 603 cases of prostate cancer-related deaths were observed. The intake of spermidine was not associated with the incidence of prostate cancer (the relative risk value between the highest quintile and the lowest quintile was 1.00, with a 95% confidence interval of 0.89-1.12). A non-linear inverse association was observed in terms of all-cause mortality (non-linear p value < 0.010). However, in the competing risk model, no significant association was found with the specific mortality rate of prostate cancer (the relative risk value of the highest quintile was 1.24, with a 95% confidence interval of 0.96-1.60, p = 0.10). CONCLUSION: Dietary spermidine intake is not associated with prostate cancer incidence or prostate cancer-specific mortality. The observed inverse association with all-cause mortality may reflect residual confounding. These findings are hypothesis-generating and do not support clinical or dietary recommendations.