On April 12, 2010, the Occupational Cancer Research Centre and the Institute for Work & Health (IWH) co-hosted a scientific symposium on the health effects of shift work. More than 100 researchers and representatives from the employer, labour and workers’ compensation communities — primarily from Ontario, but also other parts of Canada, the United States and Europe — came together in Toronto to participate in the symposium. The aim was to provide an overview from leading scientific experts on research findings about the health effects of shift work, and collectively identify the key gaps in the research evidence.
Also on this topic is an IWH Issue Briefing that provides a plain-language overview of some of the literature in this area. It was written when plans for the symposium were being developed. It is not a systematic or comprehensive review of the relevant literature, which is large and rapidly expanding.
The presentation slides, abstracts and presenter biographies are also available for the full program.
One third of the Canadian labour force does not work a regular daytime shift. Work during night, evening, and rotating shifts has the greatest potential for disturbing sleep patterns and the disruption of circadian rhythms. Shift work involving night and evenings has been associated with a wide variety of health effects, including an increased risk of workplace injury, heart disease, and cancer. These health effects may be expected to vary by both industry and sex. For example, the underlying risk of workplace injury may vary significantly by industry and the strongest evidence for cancer is for breast cancer among women. In this paper we will describe the patterns of shift work in Canada.
Based on the 2005 Survey of Labour and Income Dynamics conducted by Statistics Canada, approximately 12% of employed Canadians worked rotating shifts while 6% worked regular evenings and 2.3% worked regular night shifts. "Accommodation and food services" is the sector with the largest proportion of the labour force working these shifts (40%), but other large sectors such as "Manufacturing" and "Health care and social assistance" also have large proportions (27% and 26% respectively). In terms of absolute numbers, "Health care and social assistance" is the sector with the largest number of women (n=334,000) working rotating, evening or night shifts, closely followed by "Trade" (n=309,000) and "Accommodation and food services" (n=246,000). For men, the largest sector by far was "Manufacturing" (n=470,000), although large numbers of men were also employed in "Trade" (n=238,000) and "Accommodation and food services" (n=208,000).
The patterns of shift work in Canada vary considerably between men and women as well as between industries. It is important to understand the patterns and trends in shift work to design studies, predict health impacts, and target efforts to prevent or mitigate any adverse health effects.
Paul Demers is a Professor and the Director of the University of British Columbia’s School of Environmental Health. He is an epidemiologist whose research has primarily focused on occupational cancer, lung disease, and heart disease. His recent epidemiologic studies have included an examination of the impact of air pollution on child health and several retrospective cohort studies of firefighters, paramedics, aluminum smelter workers, and sawmill workers. He has been a member of various International Agency for Research on Cancer (IARC) Working Groups for the Evaluation of Carcinogenic Risk to Humans, including the working group that evaluated shift work in 2007. He is the director of the CAREX Canada project, a national occupational and environmental hazard surveillance program funded by the Canadian Partnership against Cancer and will be presenting shift work data from that project at this symposium. Paul has just accepted an offer to become the new director of the Occupational Cancer Research Centre in Toronto.
Work schedules involving work during the normal circardian sleep period are prevalent in most industrial economies. The consequences of these work schedules on sleep duration and sleep quality have been extensively studied.
This presentation summarizes the state of research evidence on the impact of non-traditional work schedules on sleep quality. The available studies with sleep polysomnographically recorded in shift workers indicate that sleep is reduced by 1-3 hours (5-7h of sleep duration) after a night shift and before a morning shift. The reduction mainly affects sleep stages 2 and REM. The evening shift is, however, usually around 8 hours. Across time, however, and including days off (which have never been recorded) it is doubtful whether there is a situation of chronic sleep loss. Diary and Questionnaire surveys seem to support this – a 6h sleep after the night shift for permanent night work and a little less for alternating night work. Sleepiness in terms of physiological changes has rarely been recorded but appears to be strongly increased on the night shift. This is supported by a number of field studies with repeated self-ratings of sleepiness during work and after. Also the morning shift is affected by sleepiness, but to a lesser extent. It appears that individual vulnerability to shift work is mainly linked to the sleepiness component. Sleep duration does not seem to differ much between vulnerable and tolerant shift workers and laboratory work suggests that a reduction of sleep duration to 6h should only have marginal effects on sleepiness.
Shift work disorder is now an established diagnosis based on sleep difficulties and non-restorative sleep. Fatigue is a risk factor in work injury risk associated with long duration work schedules and non-traditional work hours. The presentation will conclude with a summary of the limitations of research published to date and will propose key research priorities for the future.
Torbjörn Åkerstedt, PhD, is a Professor of Behavioral Medicine at Stockholm University and Karolinska Institutet and the Head of the Institute for Stress Research (Stockholm University). Åkerstedt has published more than 200 scientific papers on sleep regulation, work hours and health, and related areas. He is the past Secretary General of the World Federation of Sleep Medicine and Sleep Research Societies and past President of the European Sleep Research Society. He is also a co-organizer of the next biannual congress of the Working Time and Shift Work Society (a section of the ICOH) in Stockholm in 2011.
Mounting evidence supports the hypothesis that non-day shift work increases risk of breast cancer in women. The IARC has classified 'shift work' as a probable human carcinogen (2A) based on the published data. In addition, a number of other large studies are ongoing or recently finished and will be reported soon. If these also support the hypothesis, and a consensus emerges that in fact, shift does increase risk (IARC class 1 carcinogen), then it will become imperative to understand the mechanism(s) for the effect. Shift work is a necessity for many people, and will only rise in prevalence as the world increasingly operates on a 24-hour global economy. There are many possible mechanisms, two prominent of which are misalignment of melatonin rhythms, and disruption of circadian gene function. These are not mutually exclusive, and there is evidence for each from both human and laboratory research.
Richard Stevens received a B.S. in Genetics from the University of California, Berkeley, and a Ph.D. in Epidemiology from the University of Washington in Seattle. He has been working for a long time trying to help figure out why people get cancer. One of his major interests has been in the possible role of iron overload. Largely on the basis of his work, published in the Journal of National Cancer Institute and the New England Journal of Medicine, the Swedish food industry decided to cease iron fortification of flour in the early 1990s. A perplexing challenge which Stevens began to engage in the late 1970s is the confounding mystery of why breast cancer risk rises so dramatically as societies industrialize. He proposed in 1987 a radical new theory that use of electric lighting, resulting in lighted nights, might produce 'circadian disruption' causing changes in the hormones relevant to breast cancer risk, and thereby play an important role in breast cancer causation worldwide. Accumulating evidence has generally supported the theory. Women who have an occupation requiring work in the evening or at night are at higher risk; blind women have been reported to be at reduced risk; and a new study from Finland has found women who sleep longer than average have much lower risk of breast cancer. Dr. Stevens' theory has received wide scientific and public attention. For example, his work has been featured in SCIENCE NEWS (October 17, 1998 and January 7, 2006) and on the cover of the scientific journal CANCER RESEARCH (July 15, 1996) as well as cited in the March 24, 2008 issue of US News & World Report ('Turning Out the Lights' by Ben Harder), the August 20, 2007 issue of the New Yorker ('The Dark Side' by David Owen), and the August, 2008 issue of O Magazine ('Bright Lights, Big Risk for Cancer' by Catherine Guthrie).
Approximately one quarter of the workforce in North America and Europe engages in shift work requiring working at night. Those who work the night shift are exposed to artificial light-at-night, which suppresses the normal nocturnal production of melatonin, and can result in sleep disruption and deprivation. Night shift work has been associated with adverse health effects, including an increase in risk of breast cancer in women and prostate cancer in men.
A number of biological mechanisms have been proposed to explain these associations. This paper will summarize the evidence for direct action of melatonin as well as indirect action of circadian disruption on hypothesized pathways in cancer etiology. Melatonin appears to influence the regulation of gonadal function by affecting the release of gonadotropins from the pituitary. Animal and human studies have shown that melatonin can stimulate testicular testosterone or ovarian estrogen production and release, thereby perhaps affecting hormone-dependent tumors. Melatonin may also have direct effects. Pharmacological concentrations of melatonin have been shown to have a direct antiproliferative and/or apoptotic effect on cancer cells in vitro, and physiological concentrations of melatonin have been shown to exert direct oncostatic effects on cancer cell proliferation. In addition to cell cycle effects, physiological melatonin concentrations are capable of reducing the activity of telomerase in MCF-7 cells in vitro, and melatonin is able to reduce the invasive and metastatic properties of MCF-7 cells. Melatonin also has a major role as an antiestrogen in estrogen-receptor-positive human breast cancer cell proliferation by suppressing the activity of the estrogen growth response pathway. Melatonin can reduce the formation of DNA adducts, can enhance immune response, and can act as a free radical scavenger.
These mechanisms will be considered in the context of providing a framework to evaluate the totality of the evidence regarding exposure to night work and the risk of specific cancers. The presentation will conclude with a discussion of key research priorities in this field.
Scott Davis, PhD, is Professor and Chairman of the Department of Epidemiology in the School of Public Health and Community Medicine at the University of Washington and a Full Member in the Program in Epidemiology of the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center. He obtained his undergraduate degree in Biology and Chemistry from the University of New Mexico, a Master of Science in Community Health from the University of Rochester, and a Ph.D. in Epidemiology from the University of Washington. He served as a Research Associate in Epidemiology at the Radiation Effects Research Foundation in Hiroshima, Japan, from 1983-1985. Dr. Davis was a Special Fellow of the Leukemia Society of American from 1986-1987, and the recipient of a Research Career Development Award from the National Cancer Institute from 1988-1993. He is an elected member of the American Epidemiological Society, and a Fellow of the American College of Epidemiology. He served as a member of the BEIR (Biological Effects of Ionizing Radiation) VII Committee of the National Academy of Sciences, and is an elected member (Academician) of the Russian Academy of Medical Sciences. He currently serves as a member of the National Cancer Institute Board of Scientific Counselors for Clinical Sciences and Epidemiology.
His primary research focus is radiation epidemiology. For more than a decade he has directed two major research activities investigating the effects of ionizing radiation on human health. One is a series of studies in the Russian Federation of the effects of radiation exposure from the Chernobyl Power Station. These studies have focused on the risk of thyroid cancer and leukemia among children in the Bryansk Oblast, and recently have expanded to include the molecular characterization of thyroid cancer cases and a large-scale study of breast cancer. The second is a long-term follow up study of thyroid disease in persons exposed to atmospheric releases of radiation from the Hanford Nuclear Site in eastern Washington State (the Hanford Thyroid Disease Study). He has also conducted several epidemiologic studies of the possible health effects associated with exposure to power frequency magnetic fields, focusing on the risk of leukemia and breast cancer. Recently this work has expanded to include investigations of the effects of exposure to light-at-night and circadian disruption, including night shift work, on melatonin and reproductive hormones important in the etiology of breast and other hormone-related cancer. He has also maintained a long-standing interest in the etiology of the leukemias and lymphomas, and has directed epidemiologic studies of Hodgkin’s disease, non-Hodgkin’s lymphoma, and multiple myeloma.
This presentation summarizes the state of research evidence on the impact of circadian disruption on cancer risk in animals. We explore the extent to which this evidence sheds light on the cancer risk faced by shift workers.
The regular alteration in the light/dark cycle over each 24 hour period is the major synchronizer of the endogenous circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the brain in all mammals including humans. The SCN is active during the day stimulating a variety of hormonal, metabolic and behavioral responses so that internal physiology is in sync with the external environment. The inactivity of the SCN at night allows pineal gland production of melatonin, a potent anti-cancer hormone. High nocturnal blood levels of melatonin are responsible for telling all the cells of the body, including cancer cells, that it is nighttime. Changes in either the length of the day or its timing/phasing can compromise SCN activity and the pineal gland production of melatonin, a phenomenon referred to as circadian disruption. Another aspect of circadian disruption relates to the suppression of the nocturnal circadian melatonin signal resulting from the exposure of an organism to light during the night.
The central biological timing mechanism provided by the SCN, including nocturnal melatonin production, has a profound impact on the development and growth of a variety of experimental malignancies in animal models of cancer. Circadian disruption caused by either increasing the duration of daily light exposure, chronically advancing the phasing of light exposure (chronic jet lag) or light at night-induced suppression of the nocturnal circadian melatonin signal stimulates the development and growth of experimental tumors. Evidence appears to be sufficiently strong for circadian disruption-induced promotion of cancer development and growth in animal models of cancer. However, it is not currently known the extent to which alterations in the light/dark environment in the experimental setting mimic what is actually experienced by shift workers. As such, their relevance to increased cancer risk in this population remains a limitation that requires new experimental approaches. The presentation will conclude with a summary of the limitations of research published to date and will propose key research priorities for the future.
David E. Blask, Ph.D., M.D. is Professor and Head, Laboratory of Chrono-Neuroendocrine Oncology, Department of Structural and Cellular Biology, Tulane University School of Medicine, Tulane Cancer Center and Louisiana Cancer Research Consortium, New Orleans, Louisiana. For over 30 years, Dr. Blask’s research has focused on the circadian control and therapeutics of cancer by melatonin as well as the consequences of the circadian disruption of melatonin production by light at night on cancer risk. He has published over 250 journal articles, reviews, chapters and abstracts on this topic. His research has been supported by funding agencies such as the National Cancer Institute, National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences and The Edwin Pauley Foundation. He currently serves on the editorial boards of the Journal of Pineal Research, Neuroendocrinology Letters and Integrative Cancer Therapies and is a consultant for the photobiology group of the International DarkSky Association. Dr. Blask has also served as a member of the working group on shift work for the International Agency for Cancer Research of the World Health Organization.
Light at night, encountered by numerous shift workers, is emerging as an occupational risk factor. This presentation will provide an overview of evidence from the Nurses’ Health Study, (NHS, 1988) and the Nurses’ Health Study II (NHS2, 1989) concerning the health effects of exposure to light at night. The unique strengths of the NHS cohorts include a prospective study design, detailed confounder information, large size, and a high prevalence of female night workers. Limitations include the one-time assessment of shift work in NHS, loss to follow-up (though small in both cohorts), potential errors in exposure assessment, and the limited ability to study rare diseases.
Several studies in these cohorts using the shift work information have yielded valuable results for various endpoints. For cancer risk, significant associations were observed for breast, colon, and endometrial cancer risk. Moderate increases in cancer risk were observed in women who had worked rotating shifts for longer durations (i.e., 15+ years). All cancer studies within the two NHS cohorts controlled for major risk factors of each individual cancer as well as job stress and SES. Evidence from the NHS cohorts contributed to the IARC recommendation to classify night shift work a carcinogen class 2A (probable carcinogen).
Cardiovascular disease risk was also found to be elevated in nurses participating in the NHS. Bone health might be affected by night work, as well as menstrual cycle regularity and menopause, all of which have recently been studied in the NHS cohorts. Those aspects of light exposure in rotating shift workers most strongly related to circadian system response, as measured by melatonin levels in urine, is currently being evaluated in NHS2, using a circadian light meter that captures the short wavelength portion of visible light. Short wavelength light has been described to most strongly suppress melatonin levels.
Determining what aspects of shift schedules (such as shift length, frequency of rotation, number of hours worked per week) are most detrimental to health is the next frontier in shift work and disease prevention. In 2009, we have added a battery of shift work questions to the NHS2 questionnaire to assess specific aspects of the nurses’ work schedule and changes throughout their professional career. Other factors of potential relevance to circadian disruption were assessed, including morningness-eveningness and sleep duration during each of the various lifetime periods. We anticipate that future research will benefit from a clear and complete description of how work schedules differentially relate to health.
Eva Schernhammer, MD, DrPH, is an Assistant Professor in the Department of Epidemiology, Harvard Medical School. Dr. Schernhammer obtained her MD from the Medical University of Vienna, an MSc in Psychology from the University of Vienna, and a Masters degree and DrPH from the Harvard University School of Public Health. Her primary research interest is in exploring the exposures that influence the circadian system in humans and the health consequences of these exposures. Current projects study the role of clock genes in the association between shift work and cancer and melatonin's cancer preventive potential. Another research focus is to examine the role of other endogenous hormones such as IGF-I and IGFBP-3, and differences with respect to functionally different polymorphisms of these genes, and risk of breast cancer. Dr. Schernhammer is also interested in the etiology and prevention of gastrointestinal tumors and in studying the relation of Parkinson's disease with cancer etiology, to further understand biological mechanisms in the development of cancer in humans.
Currently, 25% of Canadian full-time workers aged 19-64 work some form of non-traditional work schedule. There is strong evidence that night, evening, rotating and irregular shifts are associated with an elevated risk of occupational injury. These risks are generally understood to arise from the joint influence of worker fatigue (due to sleep disturbance or long work hours) and typically lower levels of supervision and co-worker support during non-daytime work schedules.
This paper is organized in four sections: 1) a narrative review of the epidemiologic evidence for a relationship between exposure to shift work and work injury risk, 2) an assessment of the population attributable risk for work injury arising from exposure to shift work, 3) an overview of the research challenges in this field and 4) an assessment of opportunities to improve the surveillance of the risks of work injury associated with shift work.
Estimates of the population attributable fraction indicate that 6-7% of workplace injuries can be attributed to the higher risk of injury associated with shift work schedules. On the basis of this estimate, an excess of 13,000 compensated injuries (lost-time and no lost-time) to men and 20,000 compensated injuries to women in Ontario can be annually attributed to the higher risk of injury associated with shift work schedules.
Among the challenges in conducting high quality population research on the health effects of shift work are: limited information at the population level on work hours, individual work demands and the availability of supervision over the 24 hour clock, and information on the health status of workers who work regular and non-regular work schedules.
Surveillance information is a foundation for the identification of potential prevention efforts and can inform the design of more sophisticated etiologic research to understand the specific mechanisms of hazards associated with non-regular work hours. The risk of work injury arising from shift work is sufficient to justify developing methods for the routine surveillance of work hours and work injury. This presentation will conclude with a discussion of the strengths and limitations of three potential approaches to monitoring work schedules and work injury risk: 1) the use of time of injury information on workers' compensation claims, 2) the use of emergency department records containing proxy information on the time of injury and the attributable cause of injury and 3) the use of labour market panel surveys that collect information on usual work schedule and the incidence of work injury in the previous 12 month recall period.
Cameron Mustard is President and Senior Scientist at the Institute for Work & Health and a Professor in the School of Public Health, Faculty of Medicine, University of Toronto. Dr. Mustard has a background in public health sciences, with an emphasis on epidemiology and health policy. He completed his doctoral training in epidemiology, health policy and behavioral sciences at the Johns Hopkins University School of Hygiene and Public Health. Dr. Mustard has active research interests in the areas of work environments and health, the organization and delivery of health services and the adequacy and equity of disability income security programs. Dr Mustard is a past member of the Board of Directors of the Canadian Institute for Health Information where he served as Chair of the Canadian Population Health Initiative Council. He was a Fellow of the Population Health Program of the Canadian Institute for Advanced Research (1998-2003) and a past recipient of a CIHR Scientist award (1998-2003).
Shift work may be related to unfavourable changes in cardiovascular risk factors and increased risk of ischemic heart disease. A systematic review was undertaken to evaluate the epidemiologic evidence for a causal relation between shift work at night and ischemic heart disease.
A systematic search until the end of March 2008 was conducted for studies providing information on the relative risk of ischemic heart disease in relation to nightshift work. The quality of included papers was discussed with respect to design, exposure and outcome information, bias, and exposure response assessments.
Fourteen studies provided relevant information. Seven analyzed fatal events, six combined fatal and non fatal events, while one study reported separately on both types. Relative risks ranged from 0.6 to 1.4 in twelve papers while two papers reported relative risks around 2. It was characteristic that most studies based on fatal events showed no or weak associations while studies based on combined fatal and nonfatal events mostly showed modest positive associations. Negative or positive bias due to the quality of outcome or exposure information, or confounder control could not be reasonably ruled out in most studies. Five studies used years in shift work for exposure response analysis and no consistent pattern was seen.
There is limited epidemiologic evidence for a causal relation between nightshift work and ischemic heart disease. The presentation will conclude with a summary of the limitations of research published to date and will propose key research priorities for the future.
Poul Frost, MD, PhD, is affiliated with the Danish Ramazzini Centre in the Department of Occupational Medicine, Aarhus University Hospital, Denmark. Dr. Frost’s recent research has focused on shift work and health, predictors of health-related job loss, and musculoskeletal disorders.
Non-traditional work schedules are suspected to present risks to pregnant women and to fetal welbeing. Maternal hormonal disturbance arising from sleep deprivation or circadian rhythm disruption, may affect fetal growth and pregnancy complications. Two independent meta-analyses (published in 2000 and 2007) found a small adverse effect of shift work on preterm delivery (PTD) risk. However, these reviews were based on a small number of high quality studies.
In this presentation, we provide an updated systematic review of the association between shift work and PTD or baby growth retardation (SGA). We conducted a systematic search of MEDLINE using combination of keywords and MeSH terms. For each relevant paper we abstracted standard details that were used to summarize design futures and to rate their methodological quality. We calculated pooled estimates of risks for PTD and SGA in a random-effect meta-analysis.
We retrieved 23 studies reporting risk estimates for PTD or SGA among women exposed to shift work. We calculated a pooled estimates for PTD=1.158 (95%CI 1.005-1.335), but the strength of the association was attenuated by some evidence of possible publication bias and when studies with poor methodological quality (incomplete reporting, spurious exposure or potential bias) were excluded, the risk estimate was slightly reduced (1.094, 95%CI 0.948-1.263. We also observed an increased risk for SGA (=1.120, CI95% 1.025-1.224), that was confirmed after excluding poor-quality studies. We also found an increased work-absence rate among exposed women and some evidence of a beneficial effect of preventive measures taken early in pregnancy.
Our data seem to confirm small adverse effects of shift works on pregnancy outcomes, suggesting that working women should receive complete information about this potential reproductive hazard and that a change from shift work should be permitted since early in pregnancy. Evidence about others adverse reproductive outcomes will be critically discussed.
Matteo Bonzini, MD, MPH, is Assistant Professor of Occupational Health in the Faculty of Medicine of the University of Insubria in Varese, Italy. He obtained his MD from the School of Medicine at the University of Milan, and his Masters in Epidemiology from the University of Turin. Dr. Bonzini’s research interests include: shift work and pregnancy complications, air pollution exposure during pregnancy and neonatal health, occupational physical activity and pregnancy outcomes, musculoskeletal disorders, benzene exposure and cancer risk, and the genetic epidemiology of lung cancer and smoking.