The prevalence of night-shift employment is on the rise among full-time and part-time workers globally. Those engaged in night-shift work encounter various biological challenges, including exposure to artificial light during nighttime and disruptions to their circadian rhythms. These factors, along with changes in daily routines and activities, may pose significant risks to the health of night workers. Notably, the number of individuals working overtime or on night shifts has increased across various sectors, particularly in transportation, healthcare, and manufacturing. The International Agency for Research on Cancer (IARC) has classified night-shift work as probably carcinogenic to humans (IARC Group 2A). Subsequent research has identified several potential mechanisms through which night-shift work may contribute to carcinogenicity: (1) disruption of circadian rhythms, (2) suppression of melatonin levels due to nighttime light exposure, (3) physiological alterations, (4) lifestyle changes, and (5) reduced vitamin D levels resulting from inadequate sunlight exposure. Colorectal cancer (CRC) poses a significant public health challenge, ranking as the second leading cause of cancer-related death worldwide in 2020. Other than CRC, other gastrointestinal cancers are also creating a great global health issue because of their morbidity and mortality rates. In this review, we highlight the role of night shifts in disturbing circadian rhythm and how this action leads to carcinogenesis in the GI tract.

Night shift work (NSW) has been associated with cancer risk in animal studies, but epidemiological evidence remains insufficient and contradictory. This study sought to investigate the causal association between NSW and 13 common cancers using a two-sample Mendelian randomization (MR) study. Genetic variants associated with NSW were extracted from the UK Biobank and selected as instrumental variables (IVs). Genome-wide association study (GWAS) data for 13 cancers were obtained from relevant consortia and biobanks. Causality was estimated using inverse-variance weighted (IVW), MR-Egger, and weighted median (WM). Sensitivity analyses, including MR-Egger intercept tests, MR-PRESSO, leave-one-out analyses, and funnel plots, were conducted to detect pleiotropy and heterogeneity. A suggestive causal association was found between NSW duration and risks of cervical (IVW: p = 0.028) and gastric cancer (IVW: p = 0.011). No significant associations were observed for other cancers (p > 0.05). These findings suggest the need to reduce NSW duration and limit nocturnal light exposure to maintain circadian rhythms and mitigate cancer risks.

When the ancestors of modern Eurasians migrated out of Africa and interbred with Eurasian archaic hominins, namely, Neanderthals and Denisovans, DNA of archaic ancestry integrated into the genomes of anatomically modern humans. This process potentially accelerated adaptation to Eurasian environmental factors, including reduced ultraviolet radiation and increased variation in seasonal dynamics. However, whether these groups differed substantially in circadian biology and whether archaic introgression adaptively contributed to human chronotypes remain unknown. Here, we traced the evolution of chronotype based on genomes from archaic hominins and present-day humans. First, we inferred differences in circadian gene sequences, splicing, and regulation between archaic hominins and modern humans. We identified 28 circadian genes containing variants with potential to alter splicing in archaics (e.g., CLOCK, PER2, RORB, and RORC) and 16 circadian genes likely divergently regulated between present-day humans and archaic hominins, including RORA. These differences suggest the potential for introgression to modify circadian gene expression. Testing this hypothesis, we found that introgressed variants are enriched among expression quantitative trait loci for circadian genes. Supporting the functional relevance of these regulatory effects, we found that many introgressed alleles have associations with chronotype. Strikingly, the strongest introgressed effects on chronotype increase morningness, consistent with adaptations to high latitude in other species. Finally, we identified several circadian loci with evidence of adaptive introgression or latitudinal clines in allele frequency. These findings identify differences in circadian gene regulation between modern humans and archaic hominins and support the contribution of introgression via coordinated effects on variation in human chronotype.

Circadian clock dysregulation has been implicated in various types of cancer and represents an area of growing research. However, the role of the circadian clock in prostate cancer has been relatively unexplored. This literature review will highlight the potential role of circadian clock dysregulation in prostate cancer by examining molecular, epidemiologic, and clinical data. The influence of melatonin, light, night shift work, chronotherapy, and androgen independence are discussed as they relate to the existing literature on their role in prostate cancer.

When the ancestors of modern Eurasians migrated out of Africa and interbred with Eurasian archaic hominins, namely Neanderthals and Denisovans, DNA of archaic ancestry integrated into the genomes of anatomically modern humans. This process potentially accelerated adaptation to Eurasian environmental factors, including reduced ultra-violet radiation and increased variation in seasonal dynamics. However, whether these groups differed substantially in circadian biology, and whether archaic introgression adaptively contributed to human chronotypes remains unknown.

Here we traced the evolution of chronotype based on genomes from archaic hominins and present-day humans. First, we inferred differences in circadian gene sequences, splicing, and regulation between archaic hominins and modern humans. We identified 28 circadian genes containing variants with potential to alter splicing in archaics (e.g., CLOCK, PER2, RORB, RORC), and 16 circadian genes likely divergently regulated between present-day humans and archaic hominins, including RORA. These differences suggest the potential for introgression to modify circadian gene expression. Testing this hypothesis, we found that introgressed variants are enriched among eQTLs for circadian genes. Supporting the functional relevance of these regulatory effects, we found that many introgressed alleles have associations with chronotype. Strikingly, the strongest introgressed effects on chronotype increase morningness, consistent with adaptations to high latitude in other species. Finally, we identified several circadian loci with evidence of adaptive introgression or latitudinal clines in allele frequency.

These findings identify differences in circadian gene regulation between modern humans and archaic hominins and support the contribution of introgression via coordinated effects on variation in human chronotype.

In modern society, there is a growing population affected by circadian clock disruption through night shift work, artificial light-at-night exposure, and erratic eating patterns. Concurrently, the rate of cancer incidence in individuals under the age of 50 is increasing at an alarming rate, and though the precise risk factors remain undefined, the potential links between circadian clock deregulation and young-onset cancers is compelling. To explore the complex biological functions of the clock, this review will first provide a framework for the mammalian circadian clock in regulating critical cellular processes including cell cycle control, DNA damage response, DNA repair, and immunity under conditions of physiological homeostasis. Additionally, this review will deconvolute the role of the circadian clock in cancer, citing divergent evidence suggesting tissue-specific roles of the biological pacemaker in cancer types such as breast, lung, colorectal, and hepatocellular carcinoma. Recent evidence has emerged regarding the role of the clock in the intestinal epithelium, as well as new insights into how genetic and environmental disruption of the clock is linked with colorectal cancer, and the molecular underpinnings of these findings will be discussed. To place these findings within a context and framework that can be applied towards human health, a focus on how the circadian clock can be leveraged for cancer prevention and chronomedicine-based therapies will be outlined.

The timing of food intake is a key cue for circadian rhythms in humans and animals. In response to food intake, gut hormones called incretin are produced by intestinal enteroendocrine cells in a circadian rhythm that stimulates insulin secretion and regulates body weight and energy expenditure. Pregnancy is associated with the expansion of β cells, the risk of gestational diabetes mellitus, and excessive weight gain. The timing of food intake is a good way to address metabolic complications during pregnancy. The current review focuses on the circadian rhythms and biological actions of enteroendocrine hormones and their associations with pregnancy status, specifically topics like food intake and gut circadian rhythms, the circadian secretion of enteroendocrine peptides, and the effects of these factors during pregnancy.

Sleep duration is a novel and potentially modifiable risk factor for cancer. We evaluated the association of self-reported sleep duration and daytime napping with odds of colorectal and gastric cancer. We included 2008 incident colorectal cancer cases, 542 gastric cancer cases and 3622 frequency-matched population controls, recruited in the MCC-Spain case-control study (2008-2013). Sleep information, socio-demographic and lifestyle characteristics were obtained through personal interviews. Multivariable adjusted logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (CI) for cancer, across categories of sleep duration (≤ 5, 6, 7, 8, ≥ 9 hours/day), daytime napping frequency (naps/week) and duration (minutes/nap). Compared to 7 hours of sleep, long sleep was associated with increased odds of colorectal (OR≥9 hours: 1.59; 95%CI 1.30-1.94) and gastric cancer (OR≥9 hours: 1.95; 1.37-2.76); short sleep was associated with increased odds of gastric cancer (OR≤5 hours: 1.32; 0.93-1.88). Frequent and long daytime naps increased the odds of colorectal (OR6-7 naps/week, ≥30 min: 1.32; 1.14-1.54) and gastric cancer (OR6-7 naps/week, ≥30 min: 1.56; 1.21-2.02). Effects of short sleep and frequent long naps were stronger among participants with night shift-work history. Sleep and circadian disruption may jointly play a role in the etiology of colorectal and gastric cancer.

A bidirectional connection between sleep and cancer exists; however, the specific associations between individual sleep disorders and particular tumors are not very clear. An accurate assessment of sleep disorders in cancer patients is necessary to improve patient health, survival, response to therapy, quality of life, reduction of comorbidities/complications. Indeed, recent scientific evidence shows that knowledge and management of sleep disorders offer interesting therapeutic perspectives for the treatment of cancer. In light of this need, the objective of this review is to assess the evidence highlighted in the research of the last ten years on the correlation between each specific category of sleep disorder according to the International Classification of Sleep Disorders 3rd Ed. and several types of tumor based on their anatomical location (head-neck, including the brain and thyroid; lung; breast; ovary; endometrium; testes; prostate; bladder; kidney; gastrointestinal tract, subdivided into: stomach, liver, colon, pancreas; skin; bone tumors; hematological malignancies: leukemia, lymphoma, multiple myeloma, polycythemia), in order to evaluate what is currently known about: 1) sleep disorders as cancer risk factor; 2) tumors associated with the onset of sleep disorders; 3) targeted therapies of sleep disorders in cancer patients and new oncological perspectives following the evaluation of sleep.

Background: Nightshift work introduces light at night and causes circadian rhythm among night workers, who are considered to be at increased risk of cancer. However, in the last 2 years, nine population-based studies reported insignificant associations between night-shift work and cancer risks. We aimed to conduct an updated systematic review and meta-analysis to ascertain the effect of night-shift work on the incidence of cancers. Methods: Our protocol was registered in PROSPERO and complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Embase, PubMed, and Web of Science databases were used to comprehensively search studies published up to May 31, 2019. The random-effect model (Der Simonian-Laird method) was carried out to combine the risk estimates of night-shift work for cancers. The dose-response meta-analysis was performed to verify whether the association was in a dose-dependent manner. Results: Our literature searching retrieved 1,660 publications. Included in the meta-analyses were 57 eligible studies with 8,477,849 participants (mean age 55 years; 2,560,886 men, 4,220,154 women, and 1,696,809 not mentioned). The pooled results showed that night-shift work was not associated with the risk of breast cancer (OR = 1.009, 95% CI = 0.984-1.033), prostate cancer (OR = 1.027, 95% CI = 0.982-1.071), ovarian cancer (OR = 1.027, 95% CI = 0.942-1.113), pancreatic cancer (OR = 1.007, 95% CI = 0.910-1.104), colorectal cancer (OR = 1.016, 95% CI = 0.964-1.068), non-Hodgkin's lymph (OR = 1.046, 95% CI = 0.994-1.098), and stomach cancer (OR = 1.064, 95% CI = 0.971-1.157), while night-shift work was associated with a reduction of lung cancer (OR = 0.949, 95% CI = 0.903-0.996), and skin cancer (OR = 0.916, 95% CI = 0.879-0.953). The dose-response meta-analysis found that cancer risk was not significantly elevated with the increased light exposure of night- shift work. Conclusion: This systematic review of 57 observational studies did not find an overall association between ever-exposure to night-shift work and the risk of breast, prostate ovarian, pancreatic, colorectal, non-Hodgkin's lymph, and stomach cancers.

To identify the association between night shift work and the risk of various cancers with a comprehensive perspective and to explore sex differences in this association.

We searched PubMed, Embase, and Web of Science for studies on the effect of night shift work on cancer, including case-control, cohort, and nested case-control studies. We computed risk estimates with 95% confidence intervals (CIs) in a random or fixed effects model and quantified heterogeneity using the I ² statistic. Subgroup, metaregression, and sensitivity analyses were performed to explore potential sources of heterogeneity. Contour-enhanced funnel plots and the trim and fill method were used together to analyze bias. Linear dose-response analysis was used to quantitatively estimate the accumulative effect of night shift work on the risk of cancer.

Fifty-eight studies were eligible for our meta-analysis, including 5,143,838 participants. In the random effects model, the pooled odds ratio (OR) of cancers was 1.15 (95% CI = 1.08-1.22, P < 0.001; I ² = 76.2%). Night shift work increased the cancer risk in both men (OR = 1.14, 95% CI = 1.05-1.25, P = 0.003) and women (OR = 1.12, 95% CI = 1.04-1.20, P = 0.002). Subgroup analyses showed that night shift work positively increased the risk of breast (OR = 1.22, 95% CI = 1.08-1.38), prostate (OR = 1.26, 95% CI = 1.05-1.52), and digestive system (OR = 1.15, 95% CI = 1.01-1.32) cancers. For every 5 years of night shift work, the cancer risk increased by 3.2% (OR = 1.032, 95% CI = 1.013-1.051).

This is the first meta-analysis identifying the positive association between night shift work and the risk of cancer and verifying that there is no sex difference in the effect of night shift work on cancer risk. Cancer risk increases with cumulative years of night shift work.

The etiology of digestive pathologies such as irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD) and cancer is not yet fully understood. In recent years, several studies have evidenced circadian variations in mechanisms involved in digestive health. In situations of disturbed circadian rhythms (chronodisruption) where the central clock and the peripheral clocks receive incoherent signals, the synchronicity is lost producing implications for health. This lack of coordination could alter the tissue function and cause long term damage to the organs. Life habits such as sleep, physical exercise, social interaction, and feeding times are determinants for stability and integrity of circadian rhythms. In recent years, experimental and clinical studies have consistently evidenced that the alteration of circadian rhythms is associated with the development of digestive pathologies mainly linked to dismotility or changes in microbiota composition. Likewise, it seems reasonable to deep into the importance of chronodisruption as a factor that may participate in the development of pathologies such as IBS, IBD and digestive cancers. Moreover, life habits respecting circadian rhythms should be promoted for the prevention of these diseases. Further studies will allow us a better understanding of the mechanisms acting at molecular level, and the development of new therapeutic targets.

In 1950, landmark epidemiology studies by Wynder & Graham and Doll & Hill contributed to identifying smoking as a potent carcinogen. In 2007, IARC classified shiftwork involving circadian disruption (CD) as probably carcinogenic; however, epidemiological evidence in regards to the carcinogenicity of shiftwork that involves nightwork is conflicting. We hypothesize that shiftwork research is lacking chronobiological and methodological rigor and that lessons can be learned from comparison with smoking research. Herein, we provide a factual view at, and a fictional case study of, 1940s smoking research which serves as an analogy for current shiftwork research dilemmas. This analogy takes the form of limiting counting cigarettes to a particular time window (i.e. at work) rather than assessing exposures to, and doses of, accumulated smoking over 24 h, highlighting the importance of exposure and dose. Simply put, smoking insights could have been delayed or even disallowed. In conclusion, CD may be similar to smoking insofar as for quantitative measures of cumulative doses, exposures both at and off work may have to be considered. Future work must explore whether such similarity factually exists and whether CD is a cancer hazard in IARC terms.