Johnni Hansen

Increased breast cancer risk among women who work predominantly at night.

Irregular working hours, including working at night, have serious psychological and physiological effects. In a nationwide population-based case-control study, we investigated the breast cancer risk among 30- to 54-year-old Danish women who worked predominantly at night. Individual employment histories were reconstructed back to 1964 for each of 7035 women with breast cancer and their individually matched controls from the records of a nationwide pension scheme with compulsory membership. Odds ratios, including 5 years of induction time and adjusted for socio-economic status, age at the birth of first and last child and number of children, were estimated by conditional logistic regression analysis. The odds ratio for breast cancer among women who worked at night at least half of a year was 1.5 (95% confidence interval, 1.2 to 1.7), and there was a tendency to increasing odds ratio by increasing duration of nighttime employment.

Occupational exposure to carcinogens in the European Union

OBJECTIVES To construct a computer assisted information system for the estimation of the numbers of workers exposed to established and suspected human carcinogens in the member states of the European Union (EU). METHODS A database called CAREX (carcinogen exposure) was designed to provide selected exposure data and documented estimates of the number of workers exposed to carcinogens by country, carcinogen, and industry. CAREX includes data on agents evaluated by the International Agency for Research on Cancer (IARC) (all agents in groups 1 and 2A as of February 1995, and selected agents in group 2B) and on ionising radiation, displayed across the 55 industrial classes. The 1990–3 occupational exposure was estimated in two phases. Firstly, estimates were generated by the CAREX system on the basis of national labour force data and exposure prevalence estimates from two reference countries (Finland and the United States) which had the most comprehensive data available on exposures to these agents. For selected countries, these estimates were then refined by national experts in view of the perceived exposure patterns in their own countries compared with those of the reference countries. RESULTS About 32 million workers (23% of those employed) in the EU were exposed to agents covered by CAREX. At least 22 million workers were exposed to IARC group 1 carcinogens. The exposed workers had altogether 42 million exposures (1.3 mean exposures for each exposed worker). The most common exposures were solar radiation (9.1 million workers exposed at least 75% of working time), environmental tobacco smoke (7.5 million workers exposed at least 75% of working time), crystalline silica (3.2 million exposed), diesel exhaust (3.0 million), radon (2.7 million), and wood dust (2.6 million). CONCLUSION These preliminary estimates indicate that in the early 1990s, a substantial proportion of workers in the EU were exposed to carcinogens.

Risk of testicular cancer in men with abnormal semen characteristics: cohort study

Abstract Objective: To explore the associations between semen characteristics and subsequent risk of testicular cancer. Design: Cohort study. Participants: 32 442 men who had a semen analysis done at the Sperm Analysis Laboratory in Copenhagen during 1963-95. Main outcome measure: Standardised incidence ratios of testicular cancer compared with total population of Danish men. Results: Men in couples with fertility problems were more likely to develop testicular cancer than other men (89 cases, standardised incidence ratio 1.6; 95% confidence interval 1.3 to 1.9). The risk was relatively constant with increasing time between semen analysis and cancer diagnosis. Analysis according to specific semen characteristics showed that low semen concentration (standardised incidence ratio 2.3), poor motility of the spermatozoa (2.5), and high proportion of morphologically abnormal spermatozoa (3.0) were all associated with an increased risk of testicular cancer. The only other cancer group that showed increased incidence was “peritoneum and other digestive organs” (six cases; 3.7, 1.3 to 8.0). Of these, two cases were probably and two cases were possibly extragonadal germ cell tumours. Conclusions: The results point towards the existence of common aetiological factors for low semen quality and testicular cancer. Low semen quality may also be associated with increased incidence of extragonadal germ cell tumours.

Meeting Report: The Role of Environmental Lighting and Circadian Disruption in Cancer and Other Diseases

Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light–dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have direct acute effects on neuroendocrine systems, for example, in suppressing melatonin synthesis or elevating cortisol production that may have untoward long-term consequences. For these reasons, the National Institute of Environmental Health Sciences convened a workshop of a diverse group of scientists to consider how best to conduct research on possible connections between lighting and health. According to the participants in the workshop, there are three broad areas of research effort that need to be addressed. First are the basic biophysical and molecular genetic mechanisms for phototransduction for circadian, neuroendocrine, and neurobehavioral regulation. Second are the possible physiologic consequences of disrupting these circadian regulatory processes such as on hormone production, particularly melatonin, and normal and neoplastic tissue growth dynamics. Third are effects of light-induced physiologic disruption on disease occurrence and prognosis, and how prevention and treatment could be improved by application of this knowledge.

Considerations of circadian impact for defining 'shift work' in cancer studies : IARC Working Group Report.

Based on the idea that electric light at night might account for a portion of the high and rising risk of breast cancer worldwide, it was predicted long ago that women working a non-day shift would be at higher risk compared with day-working women. This hypothesis has been extended more recently to prostate cancer. On the basis of limited human evidence and sufficient evidence in experimental animals, in 2007 the International Agency for Research on Cancer (IARC) classified ‘shift work that involves circadian disruption’ as a probable human carcinogen, group 2A. A limitation of the epidemiological studies carried out to date is in the definition of ‘shift work.’ IARC convened a workshop in April 2009 to consider how ‘shift work’ should be assessed and what domains of occupational history need to be quantified for more valid studies of shift work and cancer in the future. The working group identified several major domains of non-day shifts and shift schedules that should be captured in future studies: (1) shift system (start time of shift, number of hours per day, rotating or permanent, speed and direction of a rotating system, regular or irregular); (2) years on a particular non-day shift schedule (and cumulative exposure to the shift system over the subjects working life); and (3) shift intensity (time off between successive work days on the shift schedule). The group also recognised that for further domains to be identified, more research needs to be conducted on the impact of various shift schedules and routines on physiological and circadian rhythms of workers in real-world environments.

Nested case–control study of night shift work and breast cancer risk among women in the Danish military

Objectives Growing but limited evidence suggests that night shift work is associated with breast cancer. The authors conducted a nationwide case–control study nested within a cohort of 18 551 female military employees born in 1929–1968 to investigate the risk for breast cancer after night shift work and to explore the role of leisure time sun exposure and diurnal preference. Methods The authors documented 218 cases of breast cancer (1990–2003) and selected 899 age-matched controls from the cohort by incidence density sampling. Information on shift work, sun exposure habits, diurnal preference and other potential confounders was obtained from a structured questionnaire. ORs were estimated by multivariate conditional logistic regression. Results Overall, the authors observed an adjusted OR of 1.4 (95% CI 0.9 to 2.1) among women with ever compared with never night shifts. The RR for breast cancer tended to increase with increasing number of years of night shift work (p=0.03) and with cumulative number of shifts (p=0.02),with a neutral risk for fewer than three night shifts per week. The OR for the group with the highest tertile of cumulative exposure was 2.3 (95% CI 1.2 to 4.6). The most pronounced effect of night shift work on breast cancer risk was observed in women with morning chronotype preference and intense night shifts (OR=3.9, 95% CI 1.6 to 9.5). Night shift workers tended to sunbathe more frequently than day workers. Conclusions The results indicate that frequent night shift work increases the risk for breast cancer and suggest a higher risk with longer duration of intense night shifts. Women with morning preference who worked on night shifts tended to have a higher risk than those with evening preference.

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

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.

CLOCK in Breast Tumorigenesis: Genetic, Epigenetic, and Transcriptional Profiling Analyses

The transcription factors responsible for maintaining circadian rhythm influence a variety of biological processes. Recently, it has been suggested that the core circadian genes may play a role in breast tumorigenesis, possibly by influencing hormone regulation or other pathways relevant to cancer. To evaluate this hypothesis, we conducted a genetic and epigenetic association study, as well as a transcriptional profiling array and a pathway-based network analysis. We report significant correlations between single nucleotide polymorphisms associated with the central circadian regulator CLOCK and breast cancer risk, with apparent effect modification by estrogen receptor/progesterone receptor status. We also found that hypermethylation in the CLOCK promoter reduced the risk of breast cancer, and lower levels of CLOCK expression were documented in healthy controls relative to normal or tumor tissue from patients with breast cancer. Finally, we silenced CLOCK in vitro and performed a whole-genome expression microarray and pathway analysis, which identified a cancer-relevant network of transcripts with altered expression following CLOCK gene knockdown. Our findings support the hypothesis that circadian genes influence tumorigenesis, and identify a set of circadian gene variants as candidate breast cancer susceptibility biomarkers.

Risk of breast cancer after night- and shift work: current evidence and ongoing studies in Denmark

Breast cancer is the most frequent cancer among women, and the number is increasing worldwide. This tumour is strongly associated with Western lifestyle, but the specific risk factors behind this observation are not well known. Exposure to light-at-night, including disturbance of the circadian rhythm, possibly mediated via the melatonin synthesis and clock genes, has been suggested as a contributing cause of breast cancer. Since shift- and night-time work is prevalent and increasing in modern societies, this exposure may be of public health concern, and contribute to the continuing elevation in breast cancer risk. Until now only few epidemiological studies have evaluated breast cancer risk after shift- and night- work. Although these studies are all suffering from methodological problems, especially concerning assessment of light exposure, results have consistently shown an increase in risk associated with night- and shift work. Good opportunities for epidemiological cancer research exist in Denmark, and several studies on different aspects of breast cancer, work schedules, light exposure and melatonin levels are ongoing in order to further examine different aspects of this issue.

Diabetes and the Risk of Developing Parkinson’s Disease in Denmark

OBJECTIVE Insulin contributes to normal brain function. Previous studies have suggested associations between midlife diabetes and neurodegenerative diseases, including Parkinson’s disease. Using Danish population registers, we investigated whether a history of diabetes or the use of antidiabetes drugs was associated with Parkinson’s disease. RESEARCH DESIGN AND METHODS From the nationwide Danish Hospital Register hospital records, we identified 1,931 patients with a first-time diagnosis of Parkinson’s disease between 2001 and 2006. We randomly selected 9,651 population control subjects from the Central Population Registry and density matched them by birth year and sex. Pharmacy records comprising all antidiabetes and anti-Parkinson drug prescriptions in Denmark were available. Odds ratios (ORs) were estimated by logistic regression models. RESULTS Having diabetes, as defined by one or more hospitalizations and/or outpatient visits for the condition, was associated with a 36% increased risk of developing Parkinson’s disease (OR 1.36 [95% CI 1.08–1.71]). Similarly, diabetes defined by the use of any antidiabetes medications was associated with a 35% increased Parkinson’s disease risk (1.35 [1.10–1.65]). When diabetes was defined as the use of oral antidiabetes medications, effect estimates were stronger in women (2.92 [1.34–6.36]), whereas when diabetes was defined as any antidiabetes drug prescription, patients with early-onset Parkinson’s disease were at highest risk (i.e., Parkinson’s disease diagnosed before the age of 60 years; 3.07 [1.65–5.70]). CONCLUSIONS We found that a diagnosis of, or treatment received for, diabetes was significantly associated with an increased risk of developing Parkinson’s disease, especially younger-onset Parkinson’s disease. Our results suggest a common pathophysiologic pathway between the two diseases. Future studies should take age at Parkinson’s disease onset into account.