Physical Activity and Prostate Cancer

Abstract

Prostate cancer is the most commonly diagnosed cancer among men worldwide and is characterized by substantial clinical and molecular heterogeneity. As a modifiable risk factor with far-reaching health benefits, physical activity is an important target for public health intervention. Epidemiologic studies suggest that high levels of physical activity may lower risk of prostate cancer; however, the potential biological mechanisms underlying this association are not well understood. We leveraged data from the Health Professionals Follow-up Study and the Men’s Lifestyle Validation Study to investigate methods for measurement of physical activity, quantify the association between physical activity and prostate cancer risk, and investigate the link between physical activity and gene expression alterations in prostate tissue. In Chapter 1, we used prospective follow-up data from the Health Professionals Follow-up Study to examine the association between physical activity and risk of prostate cancer defined by clinical features and TMPRSS2:ERG. We found that men engaged in high levels of vigorous activity had a 25% lower risk of developing lethal prostate cancer and 29% lower risk of developing ERG-positive prostate cancer, independent of screening history. In Chapter 2, we used whole genome mRNA expression profiling to identify pathways with differential expression by vigorous activity. We identified significant gene sets enriched in the adjacent normal tissue among men with high compared to low vigorous activity, including several cancer-related, immune system, and signal transduction pathways. In Chapter 3, we examined the validity of the current physical activity questionnaire (PAQ) by comparing it to self-reported and objective assessments. We showed moderate validity of PAQ-measured physical activity compared with doubly-labeled water, accelerometer, and self-report web-based ACT24 recalls. This dissertation shows that long-term vigorous physical activity is associated with lower risk of lethal prostate cancer and provides novel evidence for a lower risk of TMPRSS2:ERG-positive disease. Additionally, these findings suggest that physical activity may influence prostate cancer development through epigenetic alterations in the prostate tissue. Furthermore, we conclude from our validation study that, given its low cost and acceptability, the PAQ adequately captures physical activity, especially when moderate or vigorous, for use in large long term prospective studies of chronic disease risk.