scholarly journals 0025 Circadian Dysregulation of DNA Repair and Increased Endogenous and Exogenous Sensitivity to DNA Damage Precipitate Elevated Cancer Risk Associated with Night Shift Work

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A10-A10
Author(s):  
H Van Dongen ◽  
B Koritala ◽  
J E McDermott ◽  
K I Porter ◽  
O A Arshad ◽  
...  

Abstract Introduction The elevated cancer risk associated with night shift work is poorly understood. To investigate whether circadian disruption may play a role, we assessed the circadian transcriptome and its association with hallmark cancer pathways, as well as sensitivity to endogenous and exogenous sources of DNA damage, after in-laboratory simulated shift work. Methods N=14 healthy humans (aged 22-34y; 10m, 4f) were exposed to a simulated night shift schedule (daytime sleep: 10:00-18:00) or a simulated day shift schedule (nighttime sleep: 22:00-06:00) for 3 days (n=7 in each condition). After the simulated shift schedule, subjects underwent a 24h constant routine protocol, during which blood was collected every 3h. Lymphocytes were extracted from the blood samples and subjected to transcriptome analysis using a NanoString multiplex assay. We evaluated 726 mRNA cancer hallmark targets (NanoString PanCancer Pathway Panel) and 17 circadian clock genes, with 18 arrhythmic internal controls. Gene expression was analyzed for circadian rhythmicity using mixed-effects cosinor analysis. Further, lymphocytes were investigated for DNA damage using an alkaline comet assay and immunofluorescence assessment of DNA damage response biomarkers BRCA1 and γH2AX. Lymphocytes collected at 07:30 and 19:30 were also exposed to ionizing radiation (2.5Gy) and DNA damage response assessments were repeated. Results Simulated night shift caused widespread disruption of circadian rhythmicity, as measured under constant routine, for core clock genes and the transcriptome of cancer hallmark pathways. The DNA repair pathway showed significant enrichment of rhythmic genes (p<0.05) after the simulated day shift schedule only. Following simulated night shift, lymphocytes showed induction of endogenous DNA damage, with extended tail in the comet assay (p<0.001), and higher percentage of lymphocytes with BRCA1 and γH2AX foci (p<0.01). Lymphocytes collected at 19:30 showed enhanced impact of ionizing radiation as indicated by increased prevalence of cells with BRCA1 and γH2AX foci (p<0.05). Conclusion Circadian dysregulation of DNA repair mechanisms and increased sensitivity to DNA damage following night shift work may increase genomic instability and precipitate elevated cancer risk in night shift workers. Support NIH grants ES022640 and CA227381, CDMRP award W81XWH-18-1-0100, and Pacific Northwest National Laboratory BRAVE investment under DOE contract DE-AC05-76RL01830.

2013 ◽  
Vol 178 (9) ◽  
pp. 1434-1441 ◽  
Author(s):  
E. S. Schernhammer ◽  
D. Feskanich ◽  
G. Liang ◽  
J. Han

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15600-e15600
Author(s):  
Chenyu Sun ◽  
Ce Cheng ◽  
Kelly Kozma ◽  
Gopika Chandra ◽  
Na Hyun Kim ◽  
...  

e15600 Background: Globally, more than 1.8 million people were diagnosed of colorectal cancer (CRC) in 2018, with over 30% of CRC in the rectum. Shift-work, involving circadian disruption, sleep deprivation and lifestyle changes, was designated as a probable cause of cancer by The International Agency for Research on Cancer. Previous studies investigating the impact of permanent night-shift work and rotating shift-work on rectal cancer risk showed controversial results. Thus, this meta-analysis was conducted. Methods: A comprehensive literature search on PubMed was conducted to identify all relevant studies published prior to January 2021 according to the established inclusion criteria. The quality assessment was performed by the Newcastle-Ottawa Scale (NOS). The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the shift-work and rectal cancer risk. Based on heterogeneity significance, random-effect or fixed-effect model was used. Subgroup analyses were conducted to explore the night-shift and rotating-shift, respectively. Sensitivity analysis and publication bias detection were performed, and trim and fill analysis was also conducted. All statistical analyses were performed using RevMan software (version 5.3; Cochrane library) and STATA 15.0 statistical software (Stata Corp., College Station, TX), and all P values were two-tailed, the test level was 0.05. Results: Thirty-seven articles were obtained from database searching. Three articles involving 1,063 rectal cancer cases were included. All studies were considered moderate to high quality. All included studies investigated on the association between shift-work and rectal cancer risk. A statistically significant association between shift-work and increased rectal cancer risk was found (OR 1.53, 95%CI: 1.31, 1.79, P< 0.00001, I 2 = 35%). In subgroup analyses, night-shift work was associated with a non-statistically significant increased risk of rectal cancer (OR 1.25, 95%CI: 0.47, 3.32, P = 0.66, I 2 = 93%). In contrast, Rotating-shift was associated with a statistically significant increased rectal cancer risk (OR 1.35, 95%CI: 1.10, 1.65, P = 0.004, I 2 = 6%). Sensitivity analysis confirmed the stability of the result. Funnel plot, Egger's test (t = 1.69, P = 0.341), and Begg's test (z = 1.04, P = 0.296) found no publication bias of analysis. Trim and fill analysis on fixed-effect model showed the pooled OR kept stable after adding two “missing” studies (OR 1.403, 95%CI: 1.224, 1.609, P <0.05). Conclusions: The current meta-analysis demonstrates that shift-work is associated with increased rectal cancer risk. However, no association between night-shift work and rectal cancer risk was found. In contrast, association between rotating-shift work and increased rectal cancer risk was found. More original studies on this topic are needed to further explore shift-work impacts on rectal cancer risk.


2020 ◽  
Vol 10 ◽  
Author(s):  
Aishe Dun ◽  
Xuan Zhao ◽  
Xu Jin ◽  
Tao Wei ◽  
Xiang Gao ◽  
...  

2016 ◽  
Author(s):  
Michelle C Turner ◽  
Georgina Gyarmati ◽  
Gemma Castaño-Vinyals ◽  
Ana Espinosa ◽  
Kyriaki Papantoniou ◽  
...  

2011 ◽  
Vol 68 (Suppl_1) ◽  
pp. A17-A18
Author(s):  
K. Papantoniou ◽  
G. Castano-Vinyals ◽  
B. P. Gomez ◽  
J. M. Altzibar ◽  
E. Ardanaz ◽  
...  

2019 ◽  
Vol 145 (9) ◽  
pp. 2597-2599 ◽  
Author(s):  
Manolis Kogevinas ◽  
Ana Espinosa ◽  
Kyriaki Papantoniou ◽  
Nuria Aragonés ◽  
Beatriz Pérez‐Gómez ◽  
...  

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 190-190
Author(s):  
Chenyu Sun ◽  
Ce Cheng

190 Background: Globally, more than 570,000 people are diagnosed of esophageal cancer each year. Shift-work involving circadian disruption was designated as a probable cause of cancer by The International Agency for Research on Cancer. Previous studies investigating the relationship between shift-work and esophageal cancer among showed controversial results. Thus, this meta-analysis was conducted. Methods: A comprehensive literature search on PubMed was conducted to identify all relevant studies published prior to September 2020 according to the established inclusion criteria. The quality assessment was performed by the Newcastle-Ottawa Scale (NOS). The pooled odds risk (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the shift-work and esophageal cancer risk. Random-effect or fixed-effect model was used to calculate the pooled OR, based on heterogeneity significance. Subgroup analyses were conducted based on night-shift versus rotating-shift. Sensitivity analysis and publication bias detection were also performed. All statistical analyses were performed using RevMan software (version 5.3; Cochrane library) and STATA 12.0 statistical software (Stata Corp., College Station, TX), and all P values were two-tailed, the test level was 0.05. Results: 21 articles were obtained from database searching, and 9 articles were obtained from other sources. 3 articles involving 52,098 participants were included. All studies were considered moderate to high quality. All included studies investigated only males on the association between shift-work and esophageal cancer risk. A statistically significant association between shift-work and increased esophageal cancer risk among males was found (OR 2.09, 95%CI: 1.48, 2.94, P< 0.0001, I 2= 29%). In subgroup analyses, night-shift work was associated with a non-statistically significant increased risk of esophageal cancer (OR 1.56, 95%CI: 0.96, 2.53, P= 0.07, I 2= 0%). In contrast, Rotating-shift was associated with increased esophageal cancer risk (OR 2.80, 95%CI: 1.72, 4.57, P < 0.0001, I 2= 0%). Sensitivity analysis confirmed the stability of the result. Funnel plot, Egger's test, and Begg's test found no publication bias of analysis (P = 0.572). Conclusions: The current meta-analysis demonstrates that shift-work is associated with increased esophageal cancer risk for males. However, no association between night-shift work and esophageal cancer risk was found. In contrast, association between rotating-shift work and increased esophageal cancer risk was found. Original studies on females regarding shift-work and esophageal cancer risk are lacking. More original studies on this topic for both male and female are needed to further explore shift-work impacts on esophageal cancer risk.


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