Shift work with and without night shifts and breast cancer risk in a cohort study from Finland.

OBJECTIVES: To examine the association of shift work with and without night work with breast cancer among women in the public sector. METHODS: Using the Finnish Public Sector cohort study (N=33 359, mean age of 40.6 years at baseline), we investigated the associations of shift work and potential confounders with incident breast cancer. Exposure to permanent day work or shift work was defined from first two consecutive surveys from 2000, 2004, 2008 or 2012 and past information on exposure in a subcohort (n=20 786). Incident cases of breast cancer (n=1129) were retrieved from the National Cancer Register and the cohort members were followed to the end of 2016. HR and 95% CI from Cox proportional hazard regression models were calculated. RESULTS: Shift work with and without night shifts was not overall associated with breast cancer. When stratified according to age, both shift work without nights (HR 2.01, 95% CI 1.12 to 3.60) and shift work with nights (OR 2.05, 95% CI 1.04 to 4.01) were associated with an increased risk after a period of 10 years or more follow-up among women aged 50 years or older, when adjusted for age, socioeconomic status, children, smoking, alcohol and body mass index. In a subgroup with past information on exposure to shift work, the increased risk by longer exposure to shift work was not significant. CONCLUSIONS: This study provides support for an increased risk of breast cancer among elderly shift workers. However, insufficient information on exposure and intensity of night work may attenuate the risk estimates.

Effects of the combined exposure to chemicals and unusual working hours.

OBJECTIVE: Both exposure to occupational chemicals and to unusual working hours have well documented effects on health. Determination of occupational exposure limits is, however, usually based on chemical-only exposure and assumes an 8-h workday, 5 days/week and a 40-h work week. A significant proportion of the workforce is exposed to chemicals while working in other work schedules. This review thus aimed to synthesize and evaluate the scientific support for a combined effect of unusual working hours and chemical exposure and, if possible, give recommendations for OEL adjustments to account for unusual working hours. METHODS: The search for articles was made as part of the preparation of a report for the Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals. In this report, unusual working hours were categorized as shift work or extended (>8 h) working hours. Inclusion criteria were observational studies in the English language published up to November 2021 in peer-reviewed journals, with explicit metrics of exposure (chemicals and unusual working hours) and of health outcome, and which explicitly tested the association between exposure and outcome. Search engines of seven databases were used. RESULTS: Of the initially 15 400 identified papers, 9 studies published between 1985 and 2021 met the inclusion criteria, 7 of which showed significant associations. Results from a few of the studies, i.e. regarding effects of dust and endotoxin on lung function, effects of acetone on sleep quality and tiredness, effects of carbon disulphide on coronary artery disease and effects of chemicals on spontaneous abortion, suggested more pronounced effects during night shifts compared to during day shifts. DISCUSSION: The reviewed data is considered insufficient to conclude on recommendations for OEL adjustment for shift work. Suggested areas of future studies are mentioned. CONCLUSION: Further studies about the effects of the combined exposure to unusual working hours and chemical exposure are essential for risk assessment, and for recommendation of potential OEL adjustments. What is important about this paper? Effects of chemical agents at the workplace may depend not only on exposure level and duration but also on the time of exposure in relation to the circadian rhythm. This study reviewed the scientific support for a combined effect of unusual working hours and chemical exposure and revealed an obvious need for additional studies regarding the complex interplay of the two different exposures with respect to adverse health effects.

Analysis of polymorphisms in the circadian-related genes and breast cancer risk in Norwegian nurses working night shifts.

INTRODUCTION: Some studies have suggested that night work may be associated with an increased risk of breast cancer in nurses. We aimed to explore the role of circadian gene polymorphisms in the susceptibility to night work-related breast cancer risk. METHODS: We conducted a nested case-control study of Norwegian nurses comprising 563 breast cancer cases and 619 controls within a cohort of 49,402 Norwegian nurses ages 35 to 74 years. We studied 60 single-nucleotide polymorphisms (SNPs) in 17 genes involved in the regulation of the circadian rhythm in cases and controls. The data were analyzed in relation to the two exposure variables "maximum number of consecutive night shifts ever worked" and "maximum number of consecutive night shifts worked for at least 5 years." The odds of breast cancer associated with each SNP was calculated in the main effects analysis and in relation to night shift work. The statistically significant odds ratios were tested for noteworthiness using two Bayesian tests: false positive report probability (FPRP) and Bayesian false discovery probability (BFDP). RESULTS: In the main effects analysis, CC carriers of rs4238989 and GG carriers of rs3760138 in the AANAT gene had increased risk of breast cancer, whereas TT carriers of BMAL1 rs2278749 and TT carriers of CLOCK rs3749474 had reduced risk. The associations were found to be noteworthy using both the FPRP and BFDP tests. With regard to the effect of polymorphisms and night work, several significant associations were observed. After applying FPRP and BFDP in women with at least four night shifts, an increased risk of breast cancer was associated with variant alleles of SNPs in the genes AANAT (rs3760138, rs4238989), BMAL1 (rs2290035, rs2278749, rs969485) and ROR-b (rs3750420). In women with three consecutive night shifts, a reduced risk of breast cancer was associated with carriage of variant alleles of SNPs in CLOCK (rs3749474), BMAL1 (rs2278749), BMAL2 (rs2306074), CSNK1E (rs5757037), NPAS2 (rs17024926), ROR-b (rs3903529, rs3750420), MTNR1A (rs131113549) and PER3 (rs1012477). CONCLUSIONS: Significant and noteworthy associations between several polymorphisms in circadian genes, night work and breast cancer risk were found among nurses who had worked at least three consecutive night shifts.

Breast cancer among nurses: is the intensity of night work related to hormone receptor status?

The aim of this study was to investigate whether night work is related to breast cancer receptor status. The effect of night work on the risk of estrogen receptor- and progesterone receptor-defined breast cancers was evaluated in 513 nurses diagnosed with breast cancer between 1996 and 2007 and in 757 frequency-matched controls, all of whom were selected from a cohort of Norwegian nurses. Odds ratios for the exposure "duration of work with a minimum of 6 consecutive night shifts" were compared for tumor subgroups with respect to the common control group through the use of polytomous logistic regression. Statistically significant associations were observed between breast cancer and work durations of ≥ 5 years with ≥ 6 consecutive night shifts, with the highest risk observed for progesterone receptor-positive tumors (odds ratio = 2.4, 95% confidence interval: 1.3, 4.3; P-trend = 0.01). When the exposure variable was dichotomized (ever/never worked ≥ 6 consecutive night shifts), a borderline statistically significant heterogeneity (P = 0.05) was seen between progesterone receptor-positive and progesterone receptor-negative tumors in postmenopausal women. The association observed between consecutive night shifts and progesterone receptor-positive cancers suggests that progesterone could play an important role in the detrimental effects of night work.

Relationship between intensity of night shift work and antioxidant status in blood of nurses.

PURPOSE: Light-at-night exposure can disrupt the human circadian rhythm via clock gene expressions. The circadian rhythm influences antioxidant enzymes' activity and cellular mRNA levels of these enzymes. The employees working based on a shift system adjust to the changes occurring both on the cell level and on the level of the whole organism. Therefore, a question should be answered whether shift work disturbs oxidant-antioxidant balance and/or generates oxidative stress. METHODS: A cross-sectional study was conducted among nurses selected from the Local Registry of the Chamber of Nurses and Midwives in Lodz: 359 nurses worked daily only and 349 working rotating night shifts. These two groups differed significantly in respect of age (p < 0.0001), menopausal status (p < 0.0001), and current smoking habit (p = 0.02). The average total work duration was significantly shorter (12.4 years) in nurses working currently rotating night shifts who worked significantly longer on night shifts than day-workers (26.6 years). RESULTS: We found statistically significant higher red blood cell glutathione peroxidase in nurses working on night shifts (21.0 ± 4.6 vs. 20.0 ± 5.0 U/g Hb, p < 0.009) after adjusting for age, oral contraceptive hormone use, smoking, and drinking alcohol during last 24 h. Statistically significant lower vitamin A and E levels were found in the premenopausal women working in rotating system (0.690 ± 0.238 vs. 0.786 ± 0.262 µg/ml, p < 0.0001 for vitamin A and 10.93 ± 4.15 vs. 12.78 ± 4.75 µg/ml, p < 0.0001 for vitamin E). The marker of lipid peroxidation (TBARS concentration) was significantly lower in the premenopausal nurses than postmenopausal ones working day shifts only (2.06 ± 0.76 vs. 2.21 ± 0.80 nmol/ml, p < 0.038). We observed that erythrocyte GSH-Px activity rose statistically significant in nurses working more night shifts per month (p < 0.01). CONCLUSIONS: The results quoted above seem to support the existence of an association between light-at-night exposure and blood glutathione peroxidase activity in female shift workers. Nevertheless, in order to explain the mechanisms of this association, we need more studies.

Night shift work characteristics and 6-sulfatoxymelatonin (MT6s) in rotating night shift nurses and midwives.

OBJECTIVES: Synthesis of melatonin follows a circadian cycle, with high melatonin levels during the night and low levels during the day. Light exposure at night has been hypothesised as one of potential mechanisms of breast carcinogenesis in the night shift workers through inhibition of melatonin synthesis. The aim of the study was to examine a number of determinants for night shift work in relation to 6-sulfatoxymelatonin (MT6s), primary melatonin metabolite. METHODS: The cross-sectional study included 354 nurses and midwives (aged 40-60 years) currently working on rotating night shifts and 370 working days only. Data from questionnaires and 1-week diaries were used to characterise current job and total occupational history. Associations between rotating night shift work characteristics and MT6s (creatinine adjusted) in spot morning urine were tested in multiple linear regression models. RESULTS: No significant differences were found for MT6s concentrations between women currently working on rotating night shifts and those working only day shifts (means 47.2 vs 45.7 ng/mg Cr, respectively). The adjusted means among rotating night shift nurses and midwives varied depending on the department of employment, from 35.1 ng/mg Cr in neonatology to 68.2 ng/mg Cr in the orthopaedics department. Women working eight or more night shifts per month had significantly lower MT6s levels than those having fewer night shifts per month (37.9 vs 47.4 ng/mg Cr, respectively). Total night shift work history was not associated with MT6s. CONCLUSIONS: The results of this study indicate that working eight or more night shifts per month may disrupt the synthesis of melatonin.

Extended Work Shifts Increase Subjective Pain Complaints Among Cabin Crewmembers, but Not Among Airline Pilots or Healthcare Workers: A Repeated-Measures Study.

OBJECTIVE: To determine whether four consecutive extended work shifts are associated with an increased risk of subjective pain complaints, sleep duration, and sleep disturbances. METHODS: Forty-three healthcare workers, 41 cabin crewmembers, and 18 airline pilots working 4 consecutive extended workdays reported subjective pain complaints and sleep after the 1st and 4th workday. RESULTS: The risk of headache (odds ratio [OR] 21.4, 95% confidence interval [CI] 1.85 to 246.5) and pain in the hands, arms, or wrists (OR 3.78, 95% CI 1.84 to 7.76) increased after workday 4 versus workday 1 in cabin crewmembers. Sleep duration was longer (0.6 to 1.1 hours), and sleep disturbances fewer, the night before the fourth extended workday, compared with before the first workday, in all occupations. CONCLUSIONS: We found no general support for an association between extended work shifts and subjective pain, whereas sleep duration was improved, and sleep disturbances reduced after 4 consecutive extended workdays.

Night work and breast cancer risk among Norwegian nurses: assessment by different exposure metrics.

Associations between night work and breast cancer risk were investigated in a nested case-control study within a cohort of 49,402 Norwegian nurses. A total of 699 (74%) of the live cases diagnosed in 1990-2007 and 895 (65%) controls, cancer free at the time of sampling, were interviewed about work history and potential risk factors. The odds ratios for risk of breast cancer in relation to different exposure metrics were estimated by multivariate unconditional logistic regression models. No increase of risk was found after long duration of work by nurses working ≥3 night shifts per month. Small, nonsignificantly increased risks were observed for exposure to ≥30 years in hospitals or other institutions (odds ratio (OR) = 1.1), ≥12 years in schedules including night work (OR = 1.3), ≥1,007 night shifts during the lifetime (OR = 1.2), and lifetime average number of ≥4 night shifts per month (OR = 1.2). Nonsignificantly increased risks of breast cancer were observed in nurses who worked ≥5 years with ≥4 (OR = 1.4) and ≥5 (OR = 1.6) consecutive night shifts. Significantly increased risks were seen in nurses who worked ≥5 years with ≥6 consecutive night shifts (OR = 1.8, 95% confidence interval: 1.1, 2.8). The results suggest that risk may be related to number of consecutive night shifts.

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 subject's 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.

Safety incidents associated with extended working hours. A systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review to assess potential consequences of extended working hours on accidents, near-accidents, safety incidents and injuries (incidents) by considering the overall certainty of evidence. METHODS: We searched five databases systematically (Medline, Embase, PsycINFO, Web of Science, and Proquest Health and safety Science Abstract) and identified 10072 studies published until December 2020. Twenty-two studies met the inclusion criteria. We followed a systematic approach to evaluate risk of bias and synthesize results in a meta-analysis. The certainty of evidence was determined by a modified version of The Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Our analyses indicated an association between working >12 hours/day (RR: 1.24, 95%CI: 1.11, 1.40), or working >55 hours/week (RR: 1.24, 95%CI: 0.98, 1.57), and elevated risk of incidents. The certainty of evidence evaluated as low. Weak or no associations were observed for other exposure contrasts: working >8 hours/day (RR: 0.93, 95%CI: 0.72, 1.19), or working overtime (RR: 1.08, 95%CI: 0.75, 1.55), working 41-48 hours/week (RR: 1.02, 95%CI: 0.92, 1.13) or 49-54 hours/week (RR: 1.02, 95%CI: 0.97, 1.07). The certainty of evidence was evaluated as low (very low for 41-48 hours/week). CONCLUSIONS: Daily working hours >12 hours and weekly working hours exceeding 55 hours was associated and increased risk of incidents. The level of evidence was low. Hence, further high-quality research is warranted to elucidate these associations.

How to schedule night shift work in order to reduce health and safety risks.

Objectives This discussion paper aims to provide scientifically based recommendations on night shift schedules, including consecutive shifts, shift intervals and duration of shifts, which may reduce health and safety risks. Short-term physiological effects in terms of circadian disruption, inadequate sleep duration and quality, and fatigue were considered as possible links between night shift work and selected health and safety risks, namely, cancer, cardio-metabolic disease, injuries, and pregnancy-related outcomes. Method In early 2020, 15 experienced shift work researchers participated in a workshop where they identified relevant scientific literature within their main research area. Results Knowledge gaps and possible recommendations were discussed based on the current evidence. The consensus was that schedules which reduce circadian disruption may reduce cancer risk, particularly for breast cancer, and schedules that optimize sleep and reduce fatigue may reduce the occurrence of injuries. This is generally achieved with fewer consecutive night shifts, sufficient shift intervals, and shorter night shift duration. Conclusions Based on the limited, existing literature, we recommend that in order to reduce the risk of injuries and possibly breast cancer, night shift schedules have: (i) ≤3 consecutive night shifts; (ii) shift intervals of ≥11 hours; and (iii) ≤9 hours shift duration. In special cases - eg, oil rigs and other isolated workplaces with better possibilities to adapt to daytime sleep - additional or other recommendations may apply. Finally, to reduce risk of miscarriage, pregnant women should not work more than one night shift in a week.

Cardiac Autonomic Activity in Commercial Aircrew During an Actual Flight Duty Period.

BACKGROUND: The work schedules of airline crewmembers include extended workdays, compressed work periods, and limited time for recovery, which may lead to cardiovascular strain and fatigue. The aim of this study was to evaluate changes in heart rate variability (HRV) during work and sleep, and with respect to work characteristics and breaks.METHODS: We followed 49 airline crewmembers during four consecutive workdays of ≥39 h. Data included HRV measurements, a questionnaire, and sleep/work diaries. HRV parameters include root mean square of successive differences (RMSSD), standard deviation of the normal beat-to-beat differences (SDNN), and the low and high frequency ratio (LF/HF).RESULTS: The results indicate higher levels of cardiovascular strain on the 4th compared to the 1st workday, most prominent among cabin crewmembers. In this group, we observed indications of decreased cardiovascular strain by increasing duration of sleep, demonstrated by increased RMSSD (B = 2.7, 95% CI 1.6, 3.8) and SDNN (B = 4.4, 95% CI 3.0, 5.7), and decreased LF/HF (B = -0.2, 95% CI, -0.4,-0.01). Similarly, longer duration of breaks was associated with lower cardiovascular strain, indicated by increased RMSSD (B = 0.1, 95% CI 0.03, 0.1) and SDNN (B = 0.1, 95% CI 0.1, 0.1). Among pilots, increased LF/HF indicated higher cardiovascular strain in those who often or always reported of high workload (B = 4.3, 95% CI 2.3, 6.3; and B = 7.3, 95% CI 3.2, 11.4, respectively).DISCUSSION: The results support the contention that the studied work period increases cardiac strain among airline crew. Work characteristics, breaks, and sleep are associated with changes in HRV.Goffeng EM, Nordby K-C, Tarvainen M, Järvelin-Pasanen S, Wagstaff A, Skare Ø, Lie J-A. Cardiac autonomic activity in commercial aircrew during an actual flight duty period. Aerosp Med Hum Perform. 2019; 90(11):945-952.

Risk of Fatigue Among Airline Crew During 4 Consecutive Days of Flight Duty.

BACKGROUND: Airline crew are being exposed to extended workdays and compressed work periods, with quick returns between duties, implying a heightened physiological and psychological strain that may lead to sleep deprivation and fatigue. The aim of the study was assessment of the effect of an extended day of flight duty and a compressed work week with regard to recovery, cumulative fatigue, and neurobehavioral performance.METHODS: We followed 18 pilots and 41 cabin crewmembers during four consecutive days of flight duty, comprising a total of ≥ 39 h, where the first day was ≥ 10 h. Information on demographics, work characteristics, health status, and physical activity was collected at baseline. Subjects completed logs for the first and fourth workday, including the Samn-Perelli Fatigue Checklist at three time points during these workdays. Two computer-based neurobehavioral tests were completed the evening prior to the first shift, and after the first and the fourth day of the work period.RESULTS: Number of flight sectors during the work period was 10-20. Self-reported fatigue levels increased during the workdays. Neurobehavioral test-scores did not deteriorate. The effects of each additional flight sector during the work period was elevated reaction times (RT) both among cabin crewmembers (B = 5.05 ms, 95% CI 0.6, 9.5) and pilots (B = 4.95 ms, 95% CI 0.4, 9.5). Precision was unaffected.DISCUSSION: Airline pilots and cabin crewmembers seem to obtain satisfactory sleep before and during the period of 4 consecutive days. The association between multiple flight sectors and increased fatigue supports previous findings.Goffeng EM, Wagstaff A, Nordby K-C, Meland A, Goffeng LO, Skare Ø, Lilja D, Lie J-AS. Risk of fatigue among airline crew during 4 consecutive days of flight duty. Aerosp Med Hum Perform. 2019; 90(5):466-474.

Fluctuations in heart rate variability of health care workers during four consecutive extended work shifts and recovery during rest and sleep.

The aim of this study was to investigate fluctuations in heart rate variability (HRV), which reflect autonomic nervous system (ANS) function and potential psychological and physical strain, among 24 health care workers during work and sleep during four consecutive extended work shifts. Data included 24/36/12 h of HRV measurements, two logbooks, and a questionnaire. A cross-shift/cross-week design was applied. HRV was measured during work, leisure time, and sleep. The HRV data included time-domain [mean RR, SD of normal to normal R-R intervals (SDNN), and root mean square of the successive differences (RMSSD)] and frequency-domain [low frequency (LF)/high frequency (HF) ratio] parameters. HRV parameters revealed significant differences among work, leisure time, and sleep. Mean RR, RMSSD, and SDNN values were lower and the LF/HF ratio was higher on the first versus last day of the work period; however, the differences were most prominent in the morning hours. The results indicate higher levels of cardiovascular stress on the first versus fourth day of the working period, and measurements at night indicate a satisfactory recovery from the extended shifts.

Cancer risk among 43000 Norwegian nurses.

OBJECTIVES: This study evaluated the influence of occupational exposure on cancer risk among female Norwegian nurses. METHODS: A historical prospective cohort study was performed. The cohort was established from the Norwegian Board of Health's registry of nurses and included women who graduated from a nursing school before 1985. The cohort (N=43 316) was linked to the Cancer Registry of Norway. The observed number of cases was compared with the expected number on the basis of national rates. Time since first employment, period of first employment, and duration of employment were used as indicators of exposure. Poisson regression analyses were used for internal comparisons, adjusting for age, period, and fertility. RESULTS: The nurses were followed over 1473931 person-years. During the follow-up (1953-2002), 6193 cancer cases were observed. The standardized incidence ratio (SIR) for all cancers combined was close to unity. Significantly lower risks were found for cancers with a known association with alcohol and tobacco consumption and sexual activity. A significantly increased risk was found for breast cancer (SIR 1.14, 95% confidence interval (95% CI) 1.09-1.19), ovarian cancer (SIR 1.14, 95% CI 1.04-1.25), malignant melanoma (SIR 1.15, 95% CI 1.04-1.28), and borderline significant risk appeared for other skin cancer (SIR 1.12, 95% CI 0.98-1.29). A positive trend for increasing time since first exposure was found for breast cancer and malignant melanoma. CONCLUSIONS: The results indicate an association between working as a nurse and an increased risk of breast cancer and malignant melanoma. Decreased risks, found for several cancers, indicate favorable lifestyle habits among nurses.

Mechanisms of Breast Cancer in Shift Workers: DNA Methylation in Five Core Circadian Genes in Nurses Working Night Shifts.

Shift work has been suggested to be associated with breast cancer risk, and circadian disruption in shift workers is hypothesized as one of the mechanisms of increased cancer risk. There is, however, insufficient molecular evidence supporting this hypothesis. Using the quantitative methodology of pyrosequencing, epigenetic changes in 5-methyl cytosine (5mC) in five circadian genes CLOCK, BMAL1, CRY1, PER1 and PER2 in female nurses working night shift work (278 breast cancer cases, 280 controls) were analyzed. In breast cancer cases, a medium exposure to night work was associated with increased methylation levels of the CLOCK (p=0.050), BMAL1 (p=0.001) and CRY1 (p=0.040) genes, compared with controls. Within the cases, analysis of the effects of shift work on the methylation patterns showed that methylation of CRY1 was lower in those who had worked night shift and had a high exposure (p=0.006) compared with cases that had worked only days. For cases with a medium exposure to night work, an increase in BMAL1 (p=0.003) and PER1 (p=0.035) methylation was observed compared with day working (unexposed) cases. The methylation levels of the five core circadian genes were also analyzed in relation to the estrogen and progesterone receptors status of the tumors in the cases, and no correlations were observed. Furthermore, nineteen polymorphisms in the five circadian genes were assessed for their effects on the methylation levels of the respective genes, but no associations were found. In summary, our data suggest that epigenetic regulation of CLOCK, BMAL1, CRY1 and PER1 may contribute to breast cancer in shift workers.

Mechanisms of breast cancer risk in shift workers: association of telomere shortening with the duration and intensity of night work.

Occupational factors such as shiftwork and especially night work that involves disruption of the circadian rhythm may contribute to increased breast cancer risk. Circadian disruption may also affect telomere length (TL). While short TL generally is associated with increased cancer risk, its association with breast cancer risk is inconclusive. We suggest that working schedules might be an important factor in assessment of effects of TL on breast cancer risk. Moreover, telomere shortening might be a potential mechanism for night work-related breast cancer. In this study, effects of shift work on TL and its association with breast cancer risk were investigated in a nested breast cancer case-control study of Norwegian nurses. TL was assessed by qPCR in DNA from 563 breast cancer patients and 619 controls. Here, we demonstrate that TL is affected by intensive night work schedules, as work with six consecutive night for a period of more than 5 years was associated with decreased telomere lengths (-3.18, 95% CI: -6.46 to -0.58, P = 0.016). Furthermore, telomere shortening is associated with increased breast cancer risk in workers with long periods of consecutive night shifts. Thus, nurses with longer telomere lengths had a lower risk for breast cancer if they had worked more than four (OR: 0.37, 95% CI: 0.16-0.79, P = 0.014) or five (OR: 0.31, 95% CI: 0.10-0.83, P = 0.029) consecutive night shifts for a period of 5 years or more. These data suggest that telomere shortening is associated with the duration and intensity of night work and may be a contributing factor for breast cancer risk among female shift workers.

Night shift work and other determinants of estradiol, testosterone, and dehydroepiandrosterone sulfate among middle-aged nurses and midwives.

OBJECTIVES: The aims of our study were to (i) investigate the association between rotating night shift work and blood concentrations of estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) and (2) evaluate the role of their non-occupational determinants. METHODS: A cross-sectional study was conducted on 345 premenopausal and 187 postmenopausal nurses and midwives (263 women working rotating night shifts and 269 women working during days). Data from in-person interviews were used, anthropometric measurements were performed, and body mass index (BMI) and waist- to-hip ratio were calculated. Morning blood and spot urine samples were collected. Multiple linear regression models were fitted with hormone concentrations as dependent variables, and night shift work characteristics and demographic, reproductive, lifestyle and anthropometric determinants as independent variables. Modification of the effect by chronotype was examined. RESULTS: Among postmenopausal women, we observed a statistically significant positive association between the total duration of night shift work >15 years and estradiol level (P<0.05 when compared to night work duration <5 years). Night shift work characteristics were significantly associated with estradiol among morning-type postmenopausal women. The well-established associations between hormones and their major determinants, such as age and BMI, were confirmed. CONCLUSIONS: The findings of our study imply that prolonged night shift work may be associated with increased estradiol levels among postmenopausal women, especially among the morning-type postmenopausal women.

Circadian gene expression in peripheral blood leukocytes of rotating night shift nurses.

OBJECTIVE: It has been hypothesized that the underlying mechanism of elevated breast cancer risk among long-term, night-working women involves circadian genes expression alteration caused by exposure to light at night and/or irregular work hours. The aim of the present study was to determine the effect of rotating night shift work on expression of selected core circadian genes. METHODS: The cross-sectional study was conducted on 184 matched nurses and midwives, who currently work either day or rotating night shifts, to determine the effect of irregular work at night on circadian gene expression in peripheral blood leukocytes. Transcript levels of BMAL1, CLOCK, CRY1, CRY2, PER1, PER2, and PER3 were determined by means of quantitative real-time polymerase chain reaction (PCR). RESULTS: After adjusting for hour of blood collection, there were no statistically significant changes of investigated circadian genes among nurses and midwives currently working rotating night shifts compared to nurses working day shifts. The highest expression of PER1 messenger ribonucleic acid (mRNA) was observed for women currently working shifts who had worked >15 years in rotating night shift work. PER1 gene expression was associated with the lifetime duration of rotating night shift work among women currently working night shifts (P=0.04). PER1 and PER3 transcript levels in blood leukocytes were significantly down-regulated in the later versus early hours of the morning between 06.00-10.00 hours (ß-coefficient -0.226, P=0.001 and ß-coefficient -0.181, P<0.0001, respectively). CONCLUSIONS: These results suggest that current rotating night shift work does not affect circadian gene expression in human circulating leukocytes. In analysis of the peripheral clock in human studies, the hour of blood collection should be precisely specified.

Rotating night shift work and polymorphism of genes important for the regulation of circadian rhythm.

OBJECTIVE: People living in industrialized societies have developed specific working schedules during the day and at night, including permanent night shifts and rotating night shifts. The aim of this study was to examine the association between circadian polymorphisms and rotating night shift work. METHODS: This cross-sectional study comprised 709 nurses and midwives (348 current rotating and 361 current day workers). Genetic polymorphism of selected clock genes BMAL1 (rs2279287), CLOCK (rs1801260), PER1 (rs2735611), PER2 (rs2304672), PER3 (rs10462020), CRY1 (rs8192440), CRY2 (rs10838527, rs10838527) was determined using real-time polymerase chain reaction (PCR) assays. RESULTS: There were no differences in BMAL1, CLOCK, CRY2, PER1, PER2, and PER3 genotypes among nurses and midwives working rotating night and day shifts. The frequency of women with rare CRY1 TT genotype was higher in the group of rotating night shift than day workers (17.0% versus 13.9%, P=0.06). Moreover, CRY1 TT genotype was associated with the total rotating shift-work duration, compared to women rarely working night shifts. CONCLUSIONS: These results suggest that CRY1 (rs8192440) polymorphism may influence the adaptation to the rotating night shift work among nurses and midwives.