Energy Balance and Prostate Cancer

Abstract

Obesity is associated with a higher risk of advanced prostate cancer and poorer prognosis after diagnosis. Those with the same body mass index (BMI) may differ in their underlying fat distribution and metabolic health, but the impact of these sub-phenotypes on subsequent prostate cancer risk remains largely unknown. Further, physical activity after prostate cancer diagnosis may improve clinical outcomes, but no randomized trial to date has reported on physical activity and survival among prostate cancer survivors. In the absence of this data, cutting-edge methods for causal inference combined with high-quality observational data are needed to evaluate the survival impact of adhering to current guidelines for physical activity. In Chapter 1, we examined the association between body fat distribution and prostate cancer risk among Icelandic men in the AGES-Reykjavik Study. Our findings suggest that visceral and thigh subcutaneous adiposity are the most important fat depots for risk of advanced and fatal prostate cancer. Among leaner men based on BMI, visceral adiposity was the fat depot most strongly associated with both advanced and fatal prostate cancer. These findings may help elucidate underlying mechanisms and target intervention strategies. In Chapter 2, we emulated a target trial of guideline-based physical activity interventions and 10-year survival among US men with nonmetastatic prostate cancer in the Health Professionals Follow-up Study. We estimated that these men would have experienced clinically meaningful reductions in mortality had they all followed current physical activity recommendations until the development of conditions limiting physical ability. These findings may help guide clinical recommendations for prostate cancer patients and future trial design. In Chapter 3, we applied metabolomics to identify plasma metabolites associated with various adiposity measures and evaluate the association between metabolically-defined obesity and advanced prostate cancer risk. We found that BMI, waist circumference, and derived fat mass were associated with a broad range of metabolic alterations. While neither adiposity nor metabolic scores were associated with risk of advanced prostate cancer, the identified metabolites may inform future research on the mechanisms linking obesity with various disease outcomes.