Introduction In 2007 IARC classified night-shift work as probably carcinogenic to humans (2A). A new evaluation in 2019, 12 years later, resulted in a similar conclusion. It was problematic that numerous cohort studies had poor exposure assessment and population studies examining key characteristics (KCs) of carcinogens were scarce and frequently small.

Objectives I will first summarise molecular epidemiology studies and identify problems that have hampered the interpretation of KC regarding night shift and cancer. I will then discuss strategies for future studies and focus on a new exposome protocol in night shift workers in Europe (EPHOR study).

Methods/Results In the EPHOR study, we will collect individual data and repeated biological samples in 800 night and day shift workers (Spain, Sweden, Denmark, The Netherlands). Exposures of interest measured mostly with personal sensors include light and light spectrum, physical activity, sleep, body temperature, noise, the timing of activities, and some chemical exposures. We will evaluate biomarkers related to immune response, inflammation, disruption of sex-steroid hormones, melatonin and cortisol, cardiometabolic status, markers of aging e.g. telomere attrition together with untargeted omics analyses. Other outcomes of interest include obesity, diabetes, and cognitive and mental outcomes.

Conclusions Some of the endpoints examined are KCs of carcinogens, others define the circadian pattern (e.g. melatonin) and others are important for non-cancer endpoints. The circadian patterns of several markers complicate interpretation since differences between day and night working hours may reflect normal variation. Interpretation of changes in time of peak of a marker (e.g. testosterone) is also complex since on some occasions this may affect functions while in others may just indicate adaptation to a changed schedule. With its large size, standardized procedures, and multiple endpoints examined including several KCs of carcinogens, we expect that the EPHOR study should provide new knowledge on the health effects related.