Lorelei Mucci

Sc.D., M.P.H.

Harvard University

Professor of Epidemiology

PLCO (Learn more about this study)

PLCO-433

Feb 11, 2019

Light at night and prostate cancer risk and progression

The International Agency for Research on Cancer (IARC) classified night shift work as a probable (group 2A) human carcinogen in 2007, with a proposed mechanism through circadian disruption. Circadian rhythms involve oscillations of daily biochemical, physiologic, and behavioral processes that are controlled by an endogenous clock and regulate many functions in the human body, including sleep and wakefulness, hormone production, and immune activity. Animal data suggest that exposure to light at night (LAN) can disrupt circadian patterns and sleep;modulate pineal gland function to decrease melatonin secretion, leading to increased tumor growth; and negatively affect thermoregulatory and immune function. Mechanistically, light falling onto specific retinal ganglion cells at night disrupts the circadian system and triggers the pineal gland to stop the release of melatonin. Increased levels of outdoor light at night (LAN), as measured by light intensity data within a region, have been associated with increased risk of breast cancer in epidemiological studies. We and others have intriguing data on circadian disruption and prostate cancer. However, the epidemiological data on outdoor LAN and prostate cancer risk is limited. An ecological study found an association between country level exposure to LAN and higher age-standardized prostate cancer rates. A study in South Korea found a positive association between LAN and urbanization and prostate cancer, with a risk ratio of 1.73 comparing the third tertile of LAN to the first tertile of LAN. Data from the Surveillance, Epidemiology and End Results (SEER) Program found that western location within a time zone was associated with small elevated risk of prostate cancer (RR=1.04, 95% CI=1.02-1.07, p=4.8 x 10-4).
The primary goal of this project is to examine the hypothesis that men exposed to higher levels of LAN will have an increased risk of advanced or fatal prostate cancer, and have worse survival after cancer diagnosis. The PLCO, as part of the PC3 cohorts, offer a unique opportunity to study questions around circadian rhythm and prostate cancer, with adequate power and diversity to ask questions around prostate cancer survival and disparities. The cohorts in PC3 afford the ability to examine the association between LAN and prostate cancer incidence and mortality using a combination of time-varying, residence-level exposure data, and individual-level information on anthropometric, lifestyle and sociodemographic risk factors. Finally, this proposal builds off work we are currently conducting around circadian disruption and prostate cancer risk in some of the cohorts included in PC3.

Aim 1) Evaluate whether greater exposure to LAN is associated with an increased risk of overall and advanced prostate cancer, and investigate whether there are differences in the association between LAN and prostate cancer by residency.

Aim 2) Assess whether LAN is associated with an increased overall and cancer-specific mortality among men with prostate cancer, overall and by primary treatment.