Energy imbalance and prostate cancer.

In this review, the emerging evidence that excessive energy intake relative to energy expenditure increases the risk of prostate cancer is discussed. The adverse effects of energy imbalance can be inferred from an experimental study demonstrating reduced prostate tumor growth, lower circulating concentrations of insulin-like growth factor-I and decreased expression of vascular endothelial growth factor with energy restriction in transplantable tumor models. The effects of energy restriction on factors mediating greater proliferation relative to apoptosis and angiogenesis suggest that energy imbalance may act late in the carcinogenic pathway. Energy intake also has been evaluated in relation to prostate cancer risk in 23 analytic epidemiologic studies. Among studies reporting effect estimates, 8 of 14 case-control studies support a direct association [top versus bottom quantile, OR(summary) = 1.3; 95% confidence interval (CI), 1.1-1.4], but none of four cohort studies do (RR(summary) = 1.0; 95% CI, 0.8-1.2). The four case-control studies that evaluated advanced disease suggest a higher risk with higher energy intake (OR(summary) = 1.6; 95% CI, 1.2-2.0). However, none of these studies considered the balance of energy intake with body size and physical activity, the major determinants of variability in energy demand. Numerous research questions remain to be addressed, including, Which biological pathways are adversely affected by energy imbalance? Does energy imbalance act early or late in prostate carcinogenesis? What is the optimal energy balance for minimizing risk of clinically important prostate cancer? Evidence is beginning to show that energy intake in excess of expenditure may affect prostate carcinogenesis and, in particular, risk of advanced disease.