Differential genome-wide DNA methylation in association with nightshift work: From discovery to policy

Abstract

Shift work, working outside the hours of 6 a.m. to 6 p.m., is done by more than 21 million people in the United States and disproportionately done by the poor and by minorities. Many acute and chronic adverse health effects (including sleeplessness leading to injuries and accidents, cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes, and cancer) have been associated with working the nightshift. But because shift work is an integral part of our economy and unlikely to go away, owing to both the necessity of some services (e.g., hospital care, police patrol, and air traffic control) and the simple demand for around-the-clock conveniences (e.g., 24-hour grocery stores and gas stations), its prevalence, health effects, and burden on vulnerable populations makes shift work not only an exacerbating social determinant of health but a pressing public health concern. Yet scientific uncertainties remain about 1) the underlying mechanisms putting shift workers at risk for these health problems, 2) biomarkers that may help us ascertain earlier who is at greatest risk, 3) and best practices for limiting and/or mitigating shift work’s harms. As such, this dissertation was undertaken to tackle some of the unknowns in each of these areas of uncertainty. The first two chapters comprise exploratory (biomarker) analyses of DNA methylation, a potential mechanism linking shift work to cancer, among day and nightshift workers from the healthcare industry in the greater Seattle area. Chapter 1 explores the main effects of shift work on genome-wide DNA methylation among shift workers with an a priori focus on circadian genes, and Chapter 2 investigates whether DNA methylation of the top findings from Chapter 1 depends on two modifiable factors, chronotype (preference for activity in the morning or evening) and sleep duration (derived from actigraphy). Chapter 3 explores the policy landscape of the nightshift, using what we know and what we do not know about shift work and cancer as a case study. Applying the precautionary principle to motivate shared responsibility for shift work’s harms, we call for the convening of a consortium of shift work stakeholders and public deliberators to set, execute, and review the findings of a shift work research agenda aimed at speeding the discovery of mechanisms and biomarkers that can inform policy decisions to protect the lives of the many millions who work at night.