Working outside normal daytime hours is increasing worldwide and is now one of the most widespread potential carcinogenic occupational exposures. There is sufficient evidence in experimental animals that light exposure during the biologic night increases tumour growth and limited epidemiologic evidence that night shift-work cause breast cancer. Existing studies had crude definitions of shift-work and did not discriminate between shift-work systems (e.g. permanent versus rotating or evening versus night).

We performed an interview based nested case–control study within a nationwide cohort of Danish nurses, including detailed information on lifetime shift-work and potential confounders. Cases of primary breast cancer (n=310) were identified from the nationwide Danish Cancer Registry. Four control nurses were selected for each case by incidence density sampling. Odds rations (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression, with adjustment for potential confounders.

Overall, nurses who worked rotating shifts after midnight had a significantly increased OR (1.8; CI 1.2–2.8) for breast cancer compared to nurses with permanent day work. No association was found in a small group of nurses with evening work and no night work (OR=0.9; 0.4–1.9). The subgroup of nurses with periods of permanent night shift in addition to rotating night and day shifts experienced an OR of 2.9 (1.1–8.0). For nurses working after midnight compared to nurses never ending work before midnight, OR in the third tertile of cumulative number of shifts was 2.2 (1.5–3.2). In an analysis of different rotating shift systems, the highest OR (2.6; 1.8–3.8) was observed for long-term day–night rotating shifts.

The results provide further evidence that night shift-work may increase the risk for breast cancer and suggest that the largest impact on risk is associated with the most disruptive shifts. FUNDING: Danish Cancer Society and National Programme of Environmental Health Research.