Night shift work, circadian disruption and risk for hormone-related cancer in female nurses

The circadian rhythm is the 24‑hour internal clock of our body that regulates cycles of sleepiness, activity, or alertness. Disruption of the circadian rhythm can develop as a consequence of shift work. Shift work-related circadian disruption (CD) may be related to increased cancer risks, as being awake during the body’s natural sleep phase suppresses melatonin secretion, a hormone known for its anti‑proliferative effects. Therefore, with this thesis we aimed to study the potential association between CD and hormone‑related cancer risk among female shift workers using data from the nationwide prospective Nightingale Study in the Netherlands. Besides shift‑work‑related factors, other potential risk factors for cancer, including oral contraceptive use, were studied in this population. We first studied the variation in tolerance to shift work between nurses, which is related to an individual’s biological preference for mornings or evenings (“chronotype”). We evaluated associations between several measures of night shift work exposure and colorectal cancer (CRC) risk using Cox proportional hazards models. Modestly increased CRC risks were observed with higher cumulative numbers of performed night shifts and higher average numbers of consecutive night shifts per month, whereas duration of night shift work in years showed no clear association. These findings suggest that intensity‑related aspects of night shift work may be more relevant for CRC risk than duration alone. Chronotype did not affect any of these associations. No associations were observed between melanoma risk and any night shift work metric, including ever exposure, duration, cumulative number of shifts, or consecutive night shifts. Recognizing that night shift work may not capture CD comprehensively, we applied a novel, individualized exposure metric that quantifies CD as the cumulative number of hours during which work schedules (including all shift types) overlap with preferred sleep times. Over six years, shift workers experienced a median of 1,674 hours of CD. Higher cumulative CD was associated with more sleep problems, increased use of sleep medication and melatonin, and a higher prevalence of overweight. Importantly, nurses who did not perform night shifts could still experience substantial exposure to CD due to other shift types, reinforcing the added value of this refined exposure measure. We then investigated cumulative CD in relation to breast cancer risk. Among 869 incident cases identified between 2018 and 2025, no evidence was found for an increased breast cancer risk associated with high levels of cumulative CD over the preceding six years. With this thesis, we optimized methodology to assess exposure to CD, including all shift types and adjusting for chronotype, and we enhanced our understanding of health risks related to (night) shift work. Findings presented in this thesis may contribute to improved identification of vulnerable worker subgroups and may inform evidence‑based strategies to prevent cancer risk.