Shift work, which is regularly experienced by millions of individuals (approximately 15% of the US work force), is associated with increased risk of cancer. Evidence from our group and others indicates that disruption of the biological clock is a major contributing factor. Yet, the underlying mechanisms are not well understood, which hampers efforts in prevention and mitigation of this devastating health risk. Our preliminary data show that shift work schedules induce increased DNA damage and alter 24-hour rhythms in the cellular expression of molecular clock genes and DNA damage repair genes. DNA damage and repair mechanisms thus become misaligned, which enhances genomic instability and may underlie the elevated cancer risk in shift work. A logical next step would be to identify diagnostic biomarkers of misalignment between DNA damage and repair processes, and search for molecular targets to develop novel treatments. However, we must first ascertain that our preliminary data pertain to real-world shift work populations.

Therefore, in a combined field/laboratory study design, we will investigate the 24-hour expression patterns of clock genes, DNA damage repair genes, other cancer hallmark genes, and markers of DNA damage, in 34 active night and day shift workers. By comparing the night and day shift workers, we will document the molecular mechanisms involved in elevated cancer risk and identify biomarkers and candidate treatment targets in real-world night shift workers.