Elsevier

Medical Hypotheses

Volume 77, Issue 3, September 2011, Pages 430-436
Medical Hypotheses

Hypotheses for mechanisms linking shiftwork and cancer

https://doi.org/10.1016/j.mehy.2011.06.002Get rights and content

Abstract

Shift work has been associated with various adverse health outcomes. In particular, there has been a recent flourish in investigating potential cancer risk associated with working night shifts and other shift schedules. Epidemiologic studies have revealed generally weak associations due to several methodological challenges such as lack of standard classifications of shift or night work. The field also has been hindered by a lack of clarity about the possible mechanisms by which shiftwork could have an effect on cancer risk. One possible mechanism is reduced production of melatonin caused by exposure to light at night. Although there is a growing body of evidence that provides some support for this mechanism, several other mechanisms also make sense from a biological point of view. Further, the relatively weak magnitude of the associations between light at night and melatonin level suggests that multiple factors may be operating along the pathway between shift work and adverse health consequences (including cancer risk). Here we propose four additional mechanisms that should be considered for a comprehensive investigation of these potential pathways. These are: phase shift; sleep disruption; lifestyle factors (such as poor quality diets, less physical activity and higher BMI); and lower vitamin D. Consideration of all these mechanisms is necessary in order to design effective preventative workplace strategies. In developed countries, approximately 20% of the population undertake shiftwork and, while we are unlikely to be able to eliminate shiftwork from current work practices, there are aspects of shiftwork that can be modified and there may be facets of individual susceptibility that we may be able to identify and target for prevention.

Introduction

The International Agency for Research on Cancer (IARC) has categorized “shift-work that involves circadian disruption” as “probably carcinogenic to humans (Group 2A)” [1]. The IARC Working Group concluded that the experimental and mechanistic evidence, including results from different rodent models, was sufficient to conclude that there was a causal association. However, since the epidemiological evidence was considered to be limited, the conclusion of the IARC expert group was that shiftwork was “probably carcinogenic.” In terms of the epidemiologic evidence, a meta-analysis of 30 epidemiological studies in female and male flight- and shift-personnel found that relative risks for two of the most common types of cancers (breast and prostate) may be increased by some 40–70% [2]. However, while it is possible that some cancers are causally associated with shiftwork, there remain a number of problems with the existing epidemiological data. The IARC Working Group identified these as:

  • Most studies have been based on just a single profession.

  • Many had limited ability to adjust for confounders.

  • There was little ability to adjust for detection bias.

  • Definitions of shiftwork have been inconsistent and broad.

In developed countries, approximately 20% of the population undertake shiftwork [1], and we are unlikely to be able to eliminate shiftwork from current work practices. However, there are aspects of shiftwork that we can change and there may be facets of individual susceptibility that we can identify and target for prevention. Central to the development of preventive approaches is to establish which aspects of shiftwork contribute to any increased risk of cancer. As a first step, we need to clearly define the possible mechanisms by which shiftwork could have an effect. Only then are we able to design studies that can specifically discriminate between these mechanisms and allow us to identify which mechanism is responsible for any effect. Evidence-based interventions can then be designed to minimise such effects.

Section snippets

Hypotheses for mechanisms linking shiftwork and cancer

There are several candidate mechanisms identified so far from animal and in vitro experiments, and from epidemiological studies, that could provide a biological rationale for the associations between shiftwork and cancer. If these are further substantiated in well-designed epidemiological studies, they could be interpreted as reflecting a cause and effect phenomenon [3].

We have defined five possible mechanisms by which the proposed link between shiftwork and cancer might act [4]. We also need

Discussion

We have presented five possible mechanisms for how shiftwork may be related to cancer. The evidence for each of these mechanisms can be summarized as below:

  • Phase shift – animal experiments have reported links between clock gene function and tumor cell induction and growth, and epidemiological studies have shown association between clock gene polymorphisms and some cancers, however, no studies have shown that shift workers have clock gene polymorphism or gene expression linked to cancer.

Conclusions

Given the complex set of possible mechanisms and contributing factors, many of which have only gained wider attention recently, it is no surprise that the initial epidemiological studies were unable to provide strong evidence of an association between shiftwork and increased risk of cancer. Since the mechanism by which shiftwork might have its effect is not known, the best metrics for measuring “exposure dose” are difficult to quantify. Indeed the definition of shiftwork is uncertain and hence

Conflict of interest statement

None to declare.

Acknowledgements

Lin Fritschi is supported by a National Health and Medical Research Council Fellowship. Thomas C. Erren is currently appointed as visiting scholar at the University of California, Berkeley. No grants were received for this work.

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