ENVIRONMENTAL FACTORS, CIRCADIAN DISRUPTION, AND RISK OF PROSTATE CANCER IN THE HEALH PROFESSIONALS FOLLOW-UP STUDY

Abstract

Dissertation Advisor: Lorelei A. Mucci Ilkania Mercedes Chowdhury-Paulino

Environmental Factors, Circadian Disruption, and Risk of Prostate Cancer in the Health Professionals Follow-up Study

ABSTRACT

Prostate cancer is the second most commonly diagnosed cancer in men living in the U.S. and the second leading cause of cancer death. Despite this great burden, there are a limited number of known risk factors for this disease. The more widely accepted risk factors are not modifiable and include age, family history, and race. The goal of this dissertation was to identify potentially modifiable risk factors for prostate cancer that could be leveraged for primary prevention. We focused on environmental risk factors because of the observed geographic variation in prostate cancer and findings from migrant studies that elucidate the importance of the environment in prostate cancer risk. There was also a dearth of research on environmental factors and prostate cancer. In the first chapter of this dissertation, we explored whether men who live in areas of high levels of outdoor light at night (LAN) had a higher risk of prostate cancer, particularly more aggressive forms of the disease. We hypothesized that higher levels of outdoor LAN disrupted men’s circadian rhythms and in turn increased their risk of prostate cancer. We estimated baseline and cumulative time-varying outdoor LAN with ~1 km2 resolution using data from the US Defense Meteorological Satellite Program’s Operational Linescan System (DMSP-OLS), which was assigned to participants’ geocoded addresses. We used multivariable Cox models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between outdoor LAN and risk of total and fatal prostate cancer. Fatal prostate cancer was defined as death from prostate cancer, and total as any diagnosis of prostate cancer during follow-up. There was no association between the interquartile range increase in cumulative outdoor LAN and total or fatal prostate cancer in adjusted models. However, there was a positive association between baseline outdoor LAN and total prostate cancer (HR: 1.06, 95% CI:1.00,1.14) including among highly screened participants (HR: 1.11, 95% CI:1.01,1.23). In the second chapter, we assessed whether living in areas with higher levels of outdoor LAN influenced sleep outcomes, specifically sleep duration and quality. We hypothesized this as a potential mechanism by which outdoor LAN may influence circadian disruption. We assigned the DMSP-OLS levels of outdoor LAN to participant addresses and used multinomial logistic regression models to estimate odds ratios (OR) and 95% confidence intervals adjusting for individual and contextual level factors. We assessed effect modification by age, retirement status, chronotype, and urbanicity. A one IQR increase in outdoor LAN was associated with increased odds of sleeping ≤6 hours compared to 7-8 hours (OR: 1.11, 95%CI: 1.04,1.18) and lower odds of sleeping 9 or more hours compared to 7-8 hours (OR=0.90, 95% CI=0.82, 0.98) in 2012. Results were similar in 2000 and 2008 and when restricted to participants who reported a home address. In 2012, one IQR increase in outdoor LAN was associated with greater odds of having difficulty falling asleep most of the time compared to rarely/never in the whole population (OR=1.12, 95% CI=1.01, 1.24) and when restricted to those who reported a home address (OR=1.18, 95% CI=1.03, 1.34). In Chapter 3, we explored another dimension of the environment, air pollution. We studied whether men who were exposed to higher levels of PM2.5 and NO2 had a higher risk of total and fatal prostate cancer. We used spatiotemporal models to estimate PM2.5 and NO2 at all mailing addresses. For outcomes, we examined risk of total and fatal prostate cancer. Multivariable Cox models were used to estimate hazard ratios and 95% confidence intervals in single and multipollutant models. We found no association between PM2.5 and total or fatal prostate cancer. Similarly, there was no association between NO2 and total or fatal prostate cancer. There was a positive association between NO2 and total prostate cancer in nonurban areas only (HR: 1.10, 95% CI:1.00, 1.21, p-het: 0.008) and there was evidence of effect modification of NO2 and total prostate cancer by region, with the strongest association in the Midwest (HR: 1.13, 95% CI:1.01, 1.27, p-het: 0.03).