Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and risk of in situ breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI). RESULTS: After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93-1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73-0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94-1.05). CONCLUSIONS: While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies.

A positive update on COVID-19 booster vaccine willingness among Danes.

INTRODUCTION: Based on survey data from September 2021, we recently reported that an estimated 90% (weighted total) of vaccinated (completed or scheduled) adult Danes were also willing to receive a COVID-19 booster vaccine, once offered. This survey was, however, fielded before booster vaccination was recommended to the general adult population in Denmark, which may have resulted in an underestimation of booster vaccine willingness. Therefore, we conducted a follow-up survey targeting the same individuals. METHODS: The follow-up survey wave was fielded in December 2021 using the same methods as in the September 2021 wave. Using data from participants responding to both survey waves, we compared COVID-19 booster vaccine willingness between the waves by means of paired t-test. RESULTS: A total of 1,429 invitees (58%) responded to the follow-up survey. Among those, 1,324 (93%) had also responded to the initial survey on COVID-19 booster vaccine willingness. At follow-up, among the 95% reporting to be vaccinated or that COVID-19 vaccination was scheduled, a weighted proportion of 95% indicated that they were willing to receive the booster vaccine once offered. Booster vaccine willingness at follow-up (December 2021) had statistically significantly increased (p less-than 0.001) compared with the initial survey (September 2021). CONCLUSIONS: Almost all of the COVID-19-vaccinated Danes seem willing to receive a booster dose of the vaccine, which bodes very well for the COVID-19 immunisation state in Denmark. FUNDING: The study was funded by a grant from the Novo Nordisk Foundation. TRIAL REGISTRATION: not relevant.

Running on empty: a longitudinal global study of psychological well-being among runners during the COVID-19 pandemic.

OBJECTIVES: There are indications that the COVID-19 pandemic has had a profound negative effect on psychological well-being. Here, we investigated this hypothesis using longitudinal data from a large global cohort of runners, providing unprecedented leverage for understanding how the temporal development in the pandemic pressure relates to well-being across countries. DESIGN: Prospective cohort study. SETTING: Global. PARTICIPANTS: We used data from the worldwide Garmin-RUNSAFE cohort that recruited runners with a Garmin Connect account, which is used for storing running activities tracked by a Garmin device. A total of 7808 Garmin Connect users from 86 countries participated. PRIMARY AND SECONDARY OUTCOME MEASURES: From 1 August 2019 (prepandemic) to 31 December 2020, participants completed surveys every second week that included the five-item WHO Well-Being Index (WHO-5). Pandemic pressure was proxied by the number of COVID-19-related deaths per country, retrieved from the Coronavirus Resource Centre at Johns Hopkins University. Panel data regression including individual- and time-fixed effects was used to study the association between country-level COVID-19-related deaths over the past 14 days and individual-level self-reported well-being over the past 14 days. RESULTS: The 7808 participants completed a total of 125 409 WHO-5 records over the study period. We found a statistically significant inverse relationship between the number of COVID-19-related deaths and the level of psychological well-being-independent of running activity and running injuries (a reduction of 1.42 WHO-5 points per COVID-19-related death per 10 000 individuals, p<0.001). CONCLUSIONS: This study suggests that the COVID-19 pandemic has had a negative effect on the psychological well-being of the affected populations, which is concerning from a global mental health perspective.

A longitudinal study of morning, evening, and night light intensities and nocturnal sleep quality in a working population.

We aimed to investigate whether higher light intensity in the morning is associated with better nocturnal sleep quality and whether higher light intensities in the evening or night have the opposite effect. Light intensity was recorded for 7 consecutive days across the year among 317 indoor and outdoor daytime workers in Denmark (55-56° N) equipped with a personal light recorder. Participants reported sleep quality after each nocturnal sleep. Sleep quality was measured using three parameters; disturbed sleep index, awakening index, and sleep onset latency. Associations between increasing light intensities and sleep quality were analyzed using mixed effects models with participant identity as a random effect. Overall, neither white nor blue light intensities during morning, evening, or night were associated with sleep quality, awakening, or sleep onset latency of the subsequent nocturnal sleep. However, secondary analyses suggested that artificial light during the morning and day contrary to solar light may increase vulnerability to evening light exposure. Altogether, we were not able to confirm that higher morning light intensity significantly improves self-reported sleep quality or that higher evening or night light intensities impair self-reported sleep quality at exposure levels encountered during daily life in a working population in Denmark. This suggests that light intensities alone are not important for sleep quality to a degree that it is distinguishable from other important parameters in daily life settings.

COVID-19 booster vaccine willingness.

INTRODUCTION: As the protection from the COVID-19 vaccines diminishes over time, health authorities are currently considering how to maintain immunity by means of vaccine booster doses. In a recent survey, we investigated COVID-19 booster vaccine willingness among Danes, a population with a high acceptance of the initial round of COVID-19 vaccination. METHODS: The data were derived from the sixth wave of the longitudinal COVID-19 Consequences Denmark Panel Survey 2020, which included questions on booster vaccine willingness. The data from the respondents were primarily analysed using descriptive statistics. The association between age, gender, level of education, region, type of received vaccine and booster vaccine willingness was analysed using multivariate logistic regression. RESULTS: Among those reporting to be vaccinated against COVID-19 or that their vaccination was scheduled, a weighted total of 90% indicated that they were willing to receive the booster vaccine, if/once offered. The only characteristic associated with booster vaccine willingness at the set level of statistical significance (0.05) was age (increased willingness with age; adjusted odds ratio per year: 1.04, 95% confidence interval: 1.02-1.06). CONCLUSIONS: The willingness to receive a booster dose of a COVID-19 vaccine is high among Danes. If health authorities decide to offer COVID-19 booster vaccines to the young, they may consider providing specific information targeted at this population to increase uptake. FUNDING: The Novo Nordisk Foundation. TRIAL REGISTRATION: not relevant.

Adiposity and Endometrial Cancer Risk in Postmenopausal Women: A Sequential Causal Mediation Analysis.

BACKGROUND: Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity-endometrial cancer link in postmenopausal women. METHODS: We used data from a case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis. RESULTS: The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5-<25 kg/m2 was 2.51 (95% confidence interval, 1.26-5.02). The ORsNIE were 1.95 (1.01-3.74) through all biomarkers [72% proportion mediated (PM)] decomposed as: 1.35 (1.06-1.73) through pathways originating with adiponectin (33% PM); 1.13 (0.71-1.80) through inflammation beyond (the potential influence of) adiponectin (13% PM); 1.05 (0.88-1.24) through C-peptide beyond adiponectin and inflammation (5% PM); and 1.22 (0.89-1.67) through estrogens beyond preceding biomarkers (21% PM). The ORNDE not through biomarkers was 1.29 (0.54-3.09). Waist circumference gave similar results. CONCLUSIONS: Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight. IMPACT: If replicated, these results could have implications for identifying targets for intervention to reduce endometrial cancer risk in women with obesity.

Light Exposure during Days with Night, Outdoor, and Indoor Work.

OBJECTIVE: To assess light exposure during days with indoor, outdoor, and night work and days off work. METHODS: Light intensity was continuously recorded for 7 days across the year among indoor (n = 170), outdoor (n = 151), and night workers (n = 188) in Denmark (55-56°N) equipped with a personal light recorder. White light intensity, duration above 80, 1000, and 2500 lux, and proportion of red, green, and blue light was depicted by time of the day and season for work days and days off work. RESULTS: Indoor workers' average light exposure only intermittently exceeded 1000 lux during daytime working hours in summer and never in winter. During daytime working hours, most outdoor workers exceeded 2500 lux in summer and 1000 lux in winter. Night workers spent on average 10-50 min >80 lux when working night shifts. During days off work, indoor and night workers were exposed to higher light intensities than during work days and few differences were seen between indoor, outdoor, and night workers. The spectral composition of light was similar for indoor, outdoor, and night workers during days at and off work. CONCLUSION: The night workers of this study were during night hours on average exposed for a limited time to light intensities expected to suppress melatonin. The indoor workers were exposed to light levels during daylight hours that may reduce general well-being and mood, especially in winter. Outdoor workers were during summer daylight hours exposed to light levels comparable to those used for the treatment of depression.

Indoor, outdoor, and night work and blood concentrations of vitamin D and parathyroid hormone.

Objectives The aim of this study was to examine blood concentrations of 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) among indoor, outdoor, permanent and rotating night workers and the association with hours spent outdoors on and off work days. Methods Blood samples were collected from 425 workers (162 indoor, 112 outdoor, 118 rotating night and 33 permanent night workers) throughout all seasons. Serum concentrations of 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) were analyzed by isotope dilution liquid chromatography-tandem mass spectrometry (LC MS/MS) and an automated immune analyzer, respectively. Personal light exposure levels were continuously recorded and used to estimate hours spent outdoors (all workers). Results Permanent night workers had 25.3% (95% CI 11.9-36.6) lower 25OHD concentration, 4.55 (95% CI 1.39-14.94) higher odds of vitamin D insufficiency (<50 nmol/L) and 14.5% [95% confidence interval (CI) 0.1-31.1] higher PTH concentration than indoor workers. Outdoor workers had similar 25OHD concentrations but 7.5% (95% CI -0.5-14.9) lower PTH concentration compared to indoor workers. Rotating night workers 25OHD and PTH concentrations did not differ from indoor workers. Concentration of 25OHD increased by 5.2% (95% CI 1.1-9.5) per hour spent outdoor at workdays in the summer. Conclusion Clinicians should be aware that vitamin D insufficiency may be more prevalent among permanent night workers and human resources should consider the positive effect of allowing workers to spend time outdoor during work hours.

Night work, light exposure and melatonin on work days and days off.

We aimed to examine the effects of night work on salivary melatonin concentration during and subsequent to night work and the mediating role of light. We included 254 day workers and 87 night workers who were followed during 322 work days and 301 days off work. Each day was defined as the 24 hour period starting from the beginning of a night shift or from waking in the mornings with day work and days off. Light levels were recorded and synchronized with diary information (start and end of sleep and work). On average, participants provided four saliva samples per day, and these were analyzed for melatonin concentration by liquid chromatography tandem mass spectrometry (LC-MS/MS). Differences between day and night workers on work days and days off were assessed with multilevel regression models with melatonin concentration as the primary outcome. All models were stratified or adjusted by time of day. For light exposure, we estimated the total, direct and indirect effects of night work on melatonin concentrations obtaining 95% confidence intervals through bootstrapping. On work days, night workers showed 15% lower salivary melatonin concentrations compared with day workers (-15.0%; 95% CI: -31.4%; 5.2%). During the night, light exposure mediated a melatonin suppression of approximately 6% (-5.9%, 95% CI: -10.2%; -1.5%). No mediating effect of light was seen during the day time. On days off, we observed no difference in melatonin concentrations between day and night workers. These findings are in accordance with a transient and partly light-mediated effect of night work on melatonin production.

Short-term effects of night shift work on breast cancer risk: a cohort study of payroll data.

Objectives The objective was to examine if night shift work is a short-term risk factor for breast cancer, including combined estrogen receptor (ER) and human epidermal growth factor 2 (HER2) breast cancer subtypes. Methods The cohort comprised 155 540 public sector female workers in Denmark who were followed from 2007-2012. Day-to-day work-hour information was available from payroll registers and 1245 incident cases of breast cancer were identified in national cancer registries together with receptor subtype information. Results A rate ratio (RR) of 0.90 [95% confidence interval (95% CI) 0.80-1.01] was observed for workers ever working night shifts during the follow-up period compared with workers only working day shifts after adjustment for age, age at first child, parity, family history of breast or ovarian cancer, sex hormones, medications related to alcoholism, family educational level, mammography screening, and other potential confounders. Comparable results were seen for the inception population of employees with first recorded employment after 2007. Modestly increased RR were suggested for breast cancer subtypes characterized by a positive HER2 status irrespective of ER status. Conclusions These findings do not support an overall short-term effect of night shift work on breast cancer risk. Future studies should explore further the impact of HER2 status.

Response to Dr Stevens' letter ref. Visitisen et al: "Short-term effects of night shift work on breast cancer risk: a cohort study of payroll data".

We thank Dr Richard Stevens for his comments (1) on our recent article that showed no increased risk of breast cancer following recent night shift work when compared with recent day shift work (2). This finding was based on linkage of day-by-day information on working hours and breast cancer incidence data. Results are thus less likely to have been biased by differential misclassification than findings from earlier studies relying on self-report (3). We defined a night shift as ≥3 hours of work between 24:00-05:00 hours and a day shift as ≥3 hours work between 6:00-20:00 hours. This day shift definition did not exclude shifts starting before 05:00 or ending after 24:00 hours. However, this affected only 0.02% and 0.3% of all day shifts, respectively. This diminutive misclassification, that is expected to be non-differential, can hardly explain our negative findings. It is suggested that shifts that begin after 07:00 and end before 18:00 would constitute a more sensible baseline comparison group. Since the biological mechanism is not certain, it is not obvious to us if this will be a more appropriate reference than the present. However, we agree that future studies should test how different definitions of shifts affect the risk of breast cancer, which will be possible using this type of data. We only had information on working hours from 2007 and onwards, and night shift work prior to 2007 could have confounded our analyses towards no effect but only if inversely associated with night shift work in 2007 or later. We find this unlikely. Left truncation could also have biased findings towards the null. We therefore supplemented analyses of the total study population with analyses of the one-third of the population with first recorded employment in 2008 or later (the inception population). Even if the mean age was 35.5 years - and many undoubtedly had been working (with and without night shifts) prior to 2008 - this population should be less affected by such selection bias, but we observed similar risk estimates as for the total study population. Taken together, we find that our study provides rather robust evidence of no short-term breast cancer risk following recent night shift work. It must, however, be stressed that data did not allow assessment of a possible long-term risk. Reference 1. Stevens R. Letter ref. Vitisen et al: "Short-term effects of night shift work on breast cancer risk: a cohort study of payroll data". Scand J Work Environ Health. 2017;43(1):95. http://dx.doi.org/10.5271/sjweh.3607 2. Vistisen HT, Garde AH, Frydenberg M, Christiansen P, Hansen AM, Hansen J, Bonde JP, Kolstad HA. Short-term effects of night shift work on breast cancer risk: A cohort study of payroll data. Scand J Work Environ Health. 2017;43(1):59-67. http://dx.doi.org/10.5271/sjweh.3603. 3. Ijaz S, Verbeek J, Seidler A, Lindbohm ML, Ojajarvi A, Orsini N, Costa G, Neuvonen K. Night-shift work and breast cancer--a systematic review and meta-analysis. Scand J Work Environ Health. 2013 Sep 1;39(5):431-47. http://dx.doi.org/10.5271/sjweh.3371.