Case–control study of shift-work and breast cancer risk in Danish nurses: Impact of shift systems

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Abstract

Background

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).

Methods

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.

Findings

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.

Interpretation

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.

Introduction

From ancient times all species ranging from cyanobacteria to humans have been organised around the 24 h rhythm given by the rotation of the earth around the sun. In mammals, including humans, many biochemical and physiological processes, e.g. hormone secretion, cell cycle, apoptosis and gene expression, are entrained to the regular 24 h rhythm by daily periods of light exposure from dawn to dusk, and darkness in the period in between.1 Such rhythms are disrupted during periods of shift-work,2 including work during evening, night and early morning, and thereby rapid change of timing of light exposure, dietary pattern and sleep/wake cycle, some of which may be involved in carcinogenicity.1 Shift-work is increasing due to the demands of the 24-h society and night-shifts occur now in 10% to 20% of the workforce.3

In 2007, the International Agency for Research on Cancer concluded: ‘shift-work that involves circadian disruption is probably carcinogenic to humans (group 2A)’.4 This finding was based on evidence that was deemed ‘sufficient’ in animals and ‘limited’ for human breast cancer. Earlier epidemiologic studies supported an association,5 and there is an emerging understanding of biological mechanisms that could account for a causal relationship,3, 6 however, the epidemiology is limited in two ways: there are fewer than 20 pertinent studies,6 and the previously used definitions of shift work are crude and not directly comparable.3

More high-quality studies in humans are required before a more definite conclusion can be reached about whether shift-work causes breast cancer and, if so, which aspects of shift-work are most problematic. We report here the results of a nested case–control study of nurses in Denmark in which detailed information was collected on the length and frequency of work in various shift systems, including day, permanent night and rotating between day, evening and night.

Section snippets

Methods

An interview-based case–control study was nested within an established national cohort of 91,140 female members of the Danish Nurses Association, covering over 95% of nurses in Denmark.7 Information on all nurses is computerised on the basis of their unique personal identification number, which includes the date of birth and sex, and is assigned to all residents of Denmark by the Central Person Register.8 This number can be used to obtain updated computerised information on e.g. vital status,

Results

The characteristics of the control women by after-midnight shift status are shown in Table 1. Nurses who worked on after-midnight ‘graveyard’ shifts, in comparison with nurses on day shifts, had a significantly longer working life, were younger at menarche and menopause, had fewer children, were older at the birth of their first child, spent fewer hours weekly on sport, had slept fewer hours per night 10 years before the interview, and were more frequently exposed to electromagnetic fields. No

Discussion

In this nationwide case–control study of Danish nurses, we observed a significantly increased odds ratio for breast cancer when work after midnight was compared with permanent day work. Further, the odds ratio tended to increase with duration and cumulative overnight shifts. In most analyses, we observed only minor confounding. Each of these tendencies is roughly in line with the results of most previous studies of shift-work and breast cancer risk (reviewed in Ref. 6).

Increased risk for breast

Role of the funding source

The funding sources did not involve in the data collection, data analysis, manuscript writing or publication. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication.

Contributors

JH and RGS were responsible for the study design and funding. JH supervised data collection, analysed data and wrote the draft report. Both authors critically revised the final report.

Conflict of interest statement

None declared.

Acknowledgements

We received unrestricted grants from the Danish Cancer Society and from the National Programme of Environmental Health Research.

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