Rotating night shift work disrupts circadian rhythms and has been associated with obesity, metabolic syndrome, and glucose dysregulation. However, its association with type 2 diabetes remains ...unclear. Therefore, we aimed to evaluate this association in two cohorts of US women.
We followed 69,269 women aged 42-67 in Nurses' Health Study I (NHS I, 1988-2008), and 107,915 women aged 25-42 in NHS II (1989-2007) without diabetes, cardiovascular disease, and cancer at baseline. Participants were asked how long they had worked rotating night shifts (defined as at least three nights/month in addition to days and evenings in that month) at baseline. This information was updated every 2-4 years in NHS II. Self-reported type 2 diabetes was confirmed by a validated supplementary questionnaire. We documented 6,165 (NHS I) and 3,961 (NHS II) incident type 2 diabetes cases during the 18-20 years of follow-up. In the Cox proportional models adjusted for diabetes risk factors, duration of shift work was monotonically associated with an increased risk of type 2 diabetes in both cohorts. Compared with women who reported no shift work, the pooled hazard ratios (95% confidence intervals) for participants with 1-2, 3-9, 10-19, and ≥20 years of shift work were 1.05 (1.00-1.11), 1.20 (1.14-1.26), 1.40 (1.30-1.51), and 1.58 (1.43-1.74, p-value for trend <0.001), respectively. Further adjustment for updated body mass index attenuated the association, and the pooled hazard ratios were 1.03 (0.98-1.08), 1.06 (1.01-1.11), 1.10 (1.02-1.18), and 1.24 (1.13-1.37, p-value for trend <0.001).
Our results suggest that an extended period of rotating night shift work is associated with a modestly increased risk of type 2 diabetes in women, which appears to be partly mediated through body weight. Proper screening and intervention strategies in rotating night shift workers are needed for prevention of diabetes.
Prospective studies linking shift work to coronary heart disease (CHD) have been inconsistent and limited by short follow-up.
To determine whether rotating night shift work is associated with CHD ...risk.
Prospective cohort study of 189,158 initially healthy women followed up over 24 years in the Nurses' Health Studies (NHS 1988-2012: N = 73,623 and NHS2 1989-2013: N = 115,535).
Lifetime history of rotating night shift work (≥3 night shifts per month in addition to day and evening shifts) at baseline (updated every 2 to 4 years in the NHS2).
Incident CHD; ie, nonfatal myocardial infarction, CHD death, angiogram-confirmed angina pectoris, coronary artery bypass graft surgery, stents, and angioplasty.
During follow-up, 7303 incident CHD cases occurred in the NHS (mean age at baseline, 54.5 years) and 3519 in the NHS2 (mean age, 34.8 years). In multivariable-adjusted Cox proportional hazards models, increasing years of baseline rotating night shift work was associated with significantly higher CHD risk in both cohorts. In the NHS, the association between duration of shift work and CHD was stronger in the first half of follow-up than in the second half (P=.02 for interaction), suggesting waning risk after cessation of shift work. Longer time since quitting shift work was associated with decreased CHD risk among ever shift workers in the NHS2 (P<.001 for trend). table: see text
Among women who worked as registered nurses, longer duration of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk. Further research is needed to explore whether the association is related to specific work hours and individual characteristics.
To prospectively evaluate the joint association of duration of rotating night shift work and lifestyle factors with risk of type 2 diabetes risk, and to quantitatively decompose this joint ...association to rotating night shift work only, to lifestyle only, and to their interaction.
Prospective cohort study.
Nurses' Health Study (1988-2012) and Nurses' Health Study II (1991-2013).
143 410 women without type 2 diabetes, cardiovascular disease, or cancer at baseline.
Rotating night shift work was defined as at least three night shifts per month in addition to day and evening shifts in that month. Unhealthy lifestyles included current smoking, physical activity levels below 30 minutes per day at moderate to vigorous intensity, diet in the bottom three fifths of the Alternate Healthy Eating Index score, and body mass index of 25 or above.
Incident cases of type 2 diabetes were identified through self report and validated by a supplementary questionnaire.
During 22-24 years of follow-up, 10 915 cases of incident type 2 diabetes occurred. The multivariable adjusted hazard ratios for type 2 diabetes were 1.31 (95% confidence interval 1.19 to 1.44) per five year increment of duration of rotating night shift work and 2.30 (1.88 to 2.83) per unhealthy lifestyle factor (ever smoking, low diet quality, low physical activity, and overweight or obesity). For the joint association of per five year increment rotating night shift work and per unhealthy lifestyle factor with type 2 diabetes, the hazard ratio was 2.83 (2.15 to 3.73) with a significant additive interaction (P for interaction <0.001). The proportions of the joint association were 17.1% (14.0% to 20.8%) for rotating night shift work alone, 71.2% (66.9% to 75.8%) for unhealthy lifestyle alone, and 11.3% (7.3% to 17.3%) for their additive interaction.
Among female nurses, both rotating night shift work and unhealthy lifestyle were associated with a higher risk of type 2 diabetes. The excess risk of rotating night shift work combined with unhealthy lifestyle was higher than the addition of risk associated with each individual factor. These findings suggest that most cases of type 2 diabetes could be prevented by adhering to a healthy lifestyle, and the benefits could be greater in rotating night shift workers.
To examine the effects of past and current night shift work and genetic type 2 diabetes vulnerability on type 2 diabetes odds.
In the UK Biobank, we examined associations of current (
= 272,214) and ...lifetime (
= 70,480) night shift work exposure with type 2 diabetes risk (6,770 and 1,191 prevalent cases, respectively). For 180,704 and 44,141 unrelated participants of European ancestry (4,002 and 726 cases, respectively) with genetic data, we assessed whether shift work exposure modified the relationship between a genetic risk score (comprising 110 single-nucleotide polymorphisms) for type 2 diabetes and prevalent diabetes.
Compared with day workers, all current night shift workers were at higher multivariable-adjusted odds for type 2 diabetes (none or rare night shifts: odds ratio OR 1.15 95% CI 1.05-1.26; some nights: OR 1.18 95% CI 1.05-1.32; and usual nights: OR 1.44 95% CI 1.19-1.73), except current permanent night shift workers (OR 1.09 95% CI 0.93-1.27). Considering a person's lifetime work schedule and compared with never shift workers, working more night shifts per month was associated with higher type 2 diabetes odds (<3/month: OR 1.24 95% CI 0.90-1.68; 3-8/month: OR 1.11 95% CI 0.90-1.37; and >8/month: OR 1.36 95% CI 1.14-1.62;
= 0.001). The association between genetic type 2 diabetes predisposition and type 2 diabetes odds was not modified by shift work exposure.
Our findings show that night shift work, especially rotating shift work including night shifts, is associated with higher type 2 diabetes odds and that the number of night shifts worked per month appears most relevant for type 2 diabetes odds. Also, shift work exposure does not modify genetic risk for type 2 diabetes, a novel finding that warrants replication.
Objectives We examined the association of night shift work history and age when night shift work was performed with cancer and cardiovascular disease risk factors among 54 724 women in the Nurses’ ...Health Study (NHS) II. Methods We calculated age-adjusted and socioeconomic status-adjusted means and percentages for cancer and cardiovascular risk factors in 2009 across categories of night shift work history. We used multivariable-adjusted logistic regression to estimate odds ratios (ORs) and 95% CIs for key risk factors among 54 724 participants (72% ever shift workers). We further examined these associations by age (20–25, 26–35, 36–45 and 46+ years) at which shift work was performed. Results Ever night shift workers had increased odds of obesity (body mass index ≥30 kg/m2; OR=1.37, 95% CI 1.31 to 1.43); higher caffeine intake (≥131 mg/day; OR=1.16, 95% CI 1.12 to 1.22) and total calorie intake (≥1715 kcal/day; OR=1.09, 95% CI 1.04 to 1.13); current smoking (OR=1.30, 95% CI 1.19 to 1.42); and shorter sleep durations (≤7 h of sleep/day; OR=1.19, 95% CI 1.15 to 1.24) compared to never night shift workers. These estimates varied depending on age at which night work was performed, with a suggestion that night shift work before age 25 was associated with fewer risk factors compared to night shift work at older ages. Conclusions Our results indicate that night shift work may contribute to an adverse chronic disease risk profile, and that risk factors may vary depending on the age at which night shift work was performed.
Animal and human data have suggested that shift work involving circadian disruption may be carcinogenic for humans, but epidemiological evidence for colorectal cancer remains limited. We investigated ...the association of rotating night shift work and colorectal cancer risk in two prospective female cohorts, the Nurses' Health Study (NHS) and NHS2, with 24 years of follow‐up. In total, 190,810 women (NHS = 77,439; NHS2 = 113,371) were included in this analysis, and 1,965 incident colorectal cancer cases (NHS = 1,527; NHS2 = 438) were reported during followup (NHS: 1988–2012, NHS2: 1989–2013). We used Cox proportional hazards models adjusted for a wide range of potential confounders. We did not observe an association between rotating night work duration and colorectal cancer risk in these cohorts (NHS: 1–14 years: Hazard Ratio (HR) 1.04, 95% CI: 0.94, 1.16; 15+ years: HR 1.15, 95% CI: 0.95, 1.39; Ptrend = 0.14 and NHS2: 1–14 years: HR 0.81, 95% CI: 0.66, 0.99; 15+ years: HR 0.96, 95% CI: 0.56, 1.64 and Ptrend = 0.88). In subsite analysis in NHS, rectal cancer risk increased after long‐term (15+ years) rotating night shift work (proximal colon cancer: HR 1.00, 95% CI: 0.75, 1.34, Ptrend = 0.90; distal colon cancer: HR 1.27, 95% CI: 0.87, 1.85, Ptrend = 0.32; rectal cancer: HR 1.60, 95% CI: 1.09, 2.34, Ptrend = 0.02). We found no overall evidence of an association between rotating night shift work and colorectal cancer risk in these two large cohorts of nurses. Risk for rectal cancer significantly increased with shift work duration, suggesting that long‐term circadian disruption may play a role in rectal cancer development.
What's new?
Night shift work is associated with circadian rhythm disruption, sleep deprivation, and lifestyle changes. Circadian disruption in particular can lead to the deregulation of basic cellular functions, including DNA damage repair, and thus is potentially carcinogenic in humans. In the present study, involving two large prospective cohorts of nurses, no overall evidence of an association was detected between rotating night shift work and colorectal cancer risk. Risk for rectal cancer increased significantly, however, with long‐term rotating night shift work, lasting 15 or more years, suggesting that long‐term circadian disruption may play a role in rectal cancer development.
Animal and epidemiologic studies suggest that exposure to light at night (LAN) may disrupt circadian patterns and decrease nocturnal secretion of melatonin, which may disturb estrogen regulation, ...leading to increased breast cancer risk.
We examined the association between residential outdoor LAN and breast cancer incidence using data from the nationwide U.S.-based Nurses' Health Study II cohort.
We followed 109,672 women from 1989 through 2013. Cumulative LAN exposure was estimated using time-varying satellite data for a composite of persistent nighttime illumination at ∼1 km
scale for each residence during follow-up. Incident invasive breast cancer cases were confirmed by medical record review. We used Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for anthropometric, reproductive, lifestyle, and socioeconomic risk factors.
Over 2,187,425 person-years, we identified 3,549 incident breast cancer cases. Based on a fully adjusted model, the estimated HR for incident breast cancer with an interquartile range (IQR) (31.6 nW/cm
/sr) increase in cumulative average outdoor LAN was 1.05 (95% CI: 1.00, 1.11). An association between LAN and breast cancer appeared to be limited to women who were premenopausal at the time of a case HR=1.07 (95% CI: 1.01, 1.14) based on 1,973 cases vs. HR=1.00 (95% CI: 0.91, 1.09) based on 1,172 cases in postmenopausal women;
-interaction=0.08. The LAN-breast cancer association was observed only in past and current smokers at the end of follow-up HR=1.00 (95% CI: 0.94, 1.07) based on 2,215 cases in never smokers; HR=1.10 (95% CI: 1.01, 1.19) based on 1,034 cases in past smokers vs. HR=1.21 (95% CI: 1.07, 1.37) for 300 cases in current smokers;
-interaction=0.08.
Although further work is required to confirm our results and to clarify potential mechanisms, our findings suggest that exposure to residential outdoor light at night may contribute to invasive breast cancer risk. https://doi.org/10.1289/EHP935.
The CpG island methylator phenotype (CIMP) is a distinct phenotype associated with microsatellite instability (MSI) and BRAF mutation in colon cancer. Recent investigations have selected 5 promoters ...(CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1) as surrogate markers for CIMP-high. However, no study has comprehensively evaluated an expanded set of methylation markers (including these 5 markers) using a large number of tumors, or deciphered the complex clinical and molecular associations with CIMP-high determined by the validated marker panel. METHOLODOLOGY/PRINCIPAL FINDINGS: DNA methylation at 16 CpG islands the above 5 plus CDKN2A (p16), CHFR, CRABP1, HIC1, IGFBP3, MGMT, MINT1, MINT31, MLH1, p14 (CDKN2A/ARF) and WRN was quantified in 904 colorectal cancers by real-time PCR (MethyLight). In unsupervised hierarchical clustering analysis, the 5 markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1), CDKN2A, CRABP1, MINT31, MLH1, p14 and WRN were generally clustered with each other and with MSI and BRAF mutation. KRAS mutation was not clustered with any methylation marker, suggesting its association with a random methylation pattern in CIMP-low tumors. Utilizing the validated CIMP marker panel (including the 5 markers), multivariate logistic regression demonstrated that CIMP-high was independently associated with older age, proximal location, poor differentiation, MSI-high, BRAF mutation, and inversely with LINE-1 hypomethylation and beta-catenin (CTNNB1) activation. Mucinous feature, signet ring cells, and p53-negativity were associated with CIMP-high in only univariate analysis. In stratified analyses, the relations of CIMP-high with poor differentiation, KRAS mutation and LINE-1 hypomethylation significantly differed according to MSI status.
Our study provides valuable data for standardization of the use of CIMP-high-specific methylation markers. CIMP-high is independently associated with clinical and key molecular features in colorectal cancer. Our data also suggest that KRAS mutation is related with a random CpG island methylation pattern which may lead to CIMP-low tumors.
In 2007, the International Agency for Research on Cancer declared shift work that involved circadian disruption to be a "probable" carcinogen (group 2A), noting that human evidence was limited. Using ...data from 2 prospective cohort studies, the Nurses' Health Study (1988-2012; n = 78,516) and Nurses' Health Study II (1989-2013; n = 114,559), we examined associations between rotating night-shift work and breast cancer risk. In the 2 cohorts, there were a total of 9,541 incident invasive breast malignancies and 24 years of follow-up. In the Nurses' Health Study, women with 30 years or more of shift work did not have a higher risk of breast cancer (hazard ratio (HR) = 0.95, 95% confidence interval (95% CI): 0.77, 1.17; P for trend = 0.63) compared with those who never did shift work, although follow-up occurred primarily after retirement from shift work. Among participants in the Nurses' Health Study II, who were younger than participants in the other cohort, the risk of breast cancer was significantly higher in women with 20 years or more of shift work at baseline, reflecting young-adult exposure (HR = 2.15, 95% CI: 1.23, 3.73; P for trend = 0.23), and was marginally significantly higher for women with 20 years or more of cumulative shift work when we used updated exposure information (HR = 1.40, 95% CI: 1.00, 1.97; P for trend = 0.74). In conclusion, long-term rotating night-shift work was associated with a higher risk of breast cancer, particularly among women who performed shift work during young adulthood. Further studies should explore the role of shift work timing on breast cancer risk.
Background Rotating night shift work imposes circadian strain and is linked to the risk of several chronic diseases. Purpose To examine associations between rotating night shift work and all-cause; ...cardiovascular disease (CVD); and cancer mortality in a prospective cohort study of 74,862 registered U.S. nurses from the Nurses’ Health Study. Methods Lifetime rotating night shift work (defined as ≥3 nights/month) information was collected in 1988. During 22 years (1988–2010) of follow-up, 14,181 deaths were documented, including 3,062 CVD and 5,413 cancer deaths. Cox proportional hazards models estimated multivariable-adjusted hazard ratios (HRs) and 95% CIs. Results All-cause and CVD mortality were significantly increased among women with ≥5 years of rotating night shift work, compared to women who never worked night shifts. Specifically, for women with 6–14 and ≥15 years of rotating night shift work, the HRs were 1.11 (95% CI=1.06, 1.17) and 1.11 (95% CI=1.05, 1.18) for all-cause mortality and 1.19 (95% CI=1.07, 1.33) and 1.23 (95% CI=1.09, 1.38) for CVD mortality. There was no significant association between rotating night shift work and all-cancer mortality (HR≥15years =1.08, 95% CI=0.98, 1.19) or mortality of any individual cancer, with the exception of lung cancer (HR≥15years =1.25, 95% CI=1.04, 1.51). Conclusions Women working rotating night shifts for ≥5 years have a modest increase in all-cause and CVD mortality; those working ≥15 years of rotating night shift work have a modest increase in lung cancer mortality. These results add to prior evidence of a potentially detrimental effect of rotating night shift work on health and longevity.
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