Chronotype and postmenopausal breast cancer risk among women in the California Teachers Study

ABSTRACT

Chronotype is the behavioral manifestation of an individual’s underlying circadian rhythm, generally characterized by one’s propensity to sleep at a particular time during the 24 hour cycle. Evening chronotypes (“night owls”) generally suffer from worse physical and mental health compared to morning chronotypes (“morning larks”) – for reasons that have yet to be explained. One hypothesis is that evening chronotypes may be more susceptible to circadian disruption, a condition where the coordinated timing of biologic processes breaks down. The role of chronotype as an independent or modifying risk factor for cancer has not been widely explored. The objective of the current study was to evaluate the risk of breast cancer associated with chronotype in a case-control study nested within the California Teachers Study (CTS) cohort. The study population consisted of 39686 post-menopausal CTS participants who provided information on chronotype by completing a questionnaire in 2012–2013. 2719 cases of primary invasive breast cancer diagnosed from 1995/1996 through completion of the chronotype questionnaire were identified by linkage of the CTS to the California Cancer Registry. 36967 CTS participants who had remained cancer-free during this same time period served as controls. Chronotype was ascertained by responses to an abbreviated version of the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ) and was characterized into five categories: definite morning, more morning than evening, neither morning or evening, more evening than morning, definite evening. Multivariable unconditional logistic regression analyses were performed to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for each of the chronotypes, adjusted for established breast cancer risk factors. Compared to definite morning types, definite evening types had an increased risk of breast cancer with elevated ORs that were statistically significant in both the crude (OR = 1.24, 95% CI: 1.10–1.40) and fully-adjusted models (OR = 1.20, 95% CI: 1.06–1.35). The risk estimates in the fully-adjusted model for all other chronotypes did not significantly differ from one. These results suggest that evening chronotype may be an independent risk factor for breast cancer among a population of women who are not known to have engaged in any substantial night shift work. Further research in other populations of non-shift workers is warranted.     

Associations between chronotype,morbidity and mortality in the UK Biobank cohort

Later chronotype (i.e. evening preference) and later timing of sleep have been associated with greater morbidity, including higher rates of metabolic dysfunction and cardiovascular disease (CVD). However, no one has examined whether chronotype is associated with mortality risk to date. Our objective was to test the hypothesis that being an evening type is associated with increased mortality in a large cohort study, the UK Biobank. Our analysis included 433 268 adults aged 38–73 at the time of enrolment and an average 6.5-year follow-up. The primary exposure was chronotype, as assessed through a single self-reported question-defining participants as definite morning types, moderate morning types, moderate evening types or definite evening types. The primary outcomes were all-cause mortality and mortality due to CVD. Prevalent disease was also compared among the chronotype groups. Analyses were adjusted for age, sex, ethnicity, smoking, body mass index, sleep duration, socioeconomic status and comorbidities. Greater eveningness, particularly being a definite evening type, was significantly associated with a higher prevalence of all comorbidities. Comparing definite evening type to definite morning type, the associations were strongest for psychological disorders (OR 1.94, 95% CI 1.86–2.02, p = < 0.001), followed by diabetes (OR 1.30, 95% CI 1.24–1.36, p = < 0.001), neurological disorders (OR 1.25, 95% CI 1.20–1.30, p = < 0.001), gastrointestinal/abdominal disorders (OR 1.23, 95% CI 1.19–1.27, p = < 0.001) and respiratory disorders (OR 1.22, 95% CI 1.18–1.26, p = < 0.001). The total number of deaths was 10 534, out of which 2127 were due to CVD. Greater eveningness, based on chronotype as an ordinal variable, was associated with a small increased risk of all-cause mortality (HR 1.02, 95% CI 1.004–1.05, p = 0.017) and CVD mortality (HR 1.04, 95% CI 1.00–1.09, p = 0.06). Compared to definite morning types, definite evening types had significantly increased risk of all-cause mortality (HR 1.10, 95% CI 1.02–1.18, p = 0.012). This first report of increased mortality in evening types is consistent with previous reports of increased levels of cardiometabolic risk factors in this group. Mortality risk in evening types may be due to behavioural, psychological and physiological risk factors, many of which may be attributable to chronic misalignment between internal physiological timing and externally imposed timing of work and social activities. These findings suggest the need for researching possible interventions aimed at either modifying circadian rhythms in individuals or at allowing evening types greater working hour flexibility.     

The association between sleep chronotype and obesity among black and white participants of the Bogalusa Heart Study

ABSTRACT

Research indicates that sleep duration and quality are inter-related factors that contribute to obesity, but few studies have focused on sleep chronotype, representing an individual’s circadian proclivity, nor assessed these factors in racially diverse middle-aged samples. We examined the associations between chronotype and obesity among black and white men and women participating in the Bogalusa Heart Study (BHS).

Body mass index (BMI) and sleep data were available for 1,197 middle-aged men and women (mean age 48.2 ± 5.3 years) who participated in the BHS 2013–2016. Based on the reduced Morningness-Eveningness Questionnaire’s cutoff values for chronotypes, we combined ‘definitely morning’ and ‘moderately morning’ types into ‘morning’ type, ‘definitely evening’ and ‘moderately evening’ types into ‘evening’ type and kept those who were “neither” type in a separate group. We used ‘morning’ type as the referent group. Obesity was defined as a BMI ≥ 30. Multivariable logistic regression models were used to examine associations adjusting for sex, age, education, smoking, alcohol use and drug use, depression, shift work, physical activity and sleep duration.

Evening chronotype, reported by 11.1% of participants, was associated with obesity after multi-variable adjustment, including shift work, physical activity and sleep duration (OR 1.67, 95% CI: 1.08–2.56). However, once stratified by race (black/white), this association was found only among white participants (OR = 1.91, 95% CI = 1.12–3.25) after full adjustment.

In our biracial, community-based population, evening chronotype was independently associated with obesity, specifically among white participants. Further research is needed to identify behavioral, endocrine, nutritional and genetic pathways which underlie these associations.     

Long-term consistency of diurnal-type preferences among men

Diurnal type (chronotype) differentiates individuals on an axis between the extremes of evening type to morning type. These diurnal-type preferences are thought to be relatively stable, but follow-up studies are sparse. The study aims were (1) to compare cross-sectional studies of diurnal type preferences between two decades and (2) to analyze the consistency of diurnal-type preferences using a longitudinal dataset. We analyzed a total of 18?087 adult males from four datasets with information on diurnal type and age. Of these, 2144 were available for survival analysis and 567 for analysis of longitudinal diurnal consistency. Diurnal type was assessed by asking the individual to what extent they would rate themselves a morning or an evening person, categorized into four groups. Statistical tests for stability of diurnal type were based on transition matrices and p values obtained using likelihood ratios. Cox regression was used to calculate the relative risk of all-cause mortality in each of the four diurnal type groups. After direct age standardization, 9.5% (95% CI: 9.0–10.1%) of participants in the four datasets were evening types. The cross-sectional data yielded that morning types were less common in the 2000s than two decades earlier. The longitudinal dataset revealed a significant shift from evening type to another type from 1985 to 2008 (p?=?0.002). The relative risk of all-cause mortality was 1.3-fold (95% CI: 1.0–1.6; p?=?0.05) higher for evening types compared to morning types. At the population level, eveningness appears to have become more prevalent over recent decades. However, on the individual level, the more morningness the chronotype, the more persistent it remains with aging.     

Bedtime misalignment and progression of breast cancer

Disruption of circadian rhythms, which frequently occurs during night shift work, may be associated with cancer progression. The effect of chronotype (preference for behaviors such as sleep, work, or exercise to occur at particular times of day, with an associated difference in circadian physiology) and alignment of bedtime (preferred vs. habitual), however, have not yet been studied in the context of cancer progression in women with breast cancer. Chronotype and alignment of actual bedtime with preferred chronotype were examined using the Morningness–Eveningness Scale (MEQ) and sleep-wake log among 85 women with metastatic breast cancer. Their association with disease-free interval (DFI) was retrospectively examined using the Cox proportional hazards model. Median DFI was 81.9 months for women with aligned bedtimes (“going to bed at preferred bedtime”) (n?=?72), and 46.9 months for women with misaligned bedtimes (“going to bed later or earlier than the preferred bedtime”) (n?=?13) (log rank p?=?0.001). In a multivariate Cox proportional hazard model, after controlling for other significant predictors of DFI, including chronotype (morning type/longer DFI; HR?=?0.539, 95% CI?=?0.320–0.906, p?=?0.021), estrogen receptor (ER) status at initial diagnosis (negative/shorter DFI; HR?=?2.169, 95% CI?=?1.124–4.187, p?=?0.028) and level of natural-killer cell count (lower levels/shorter DFI; HR?=?1.641, 95% CI?=?1.000–2.695, p?=?0.050), misaligned bedtimes was associated with shorter DFI, compared to aligned bedtimes (HR?=?3.180, 95% CI?=?1.327–7.616, p?=?0.018). Our data indicate that a misalignment of bedtime on a daily basis, an indication of circadian disruption, is associated with more rapid breast cancer progression as measured by DFI. Considering the limitations of small sample size and study design, a prospective study with a larger sample is necessary to explore their causal relationship and underlying mechanisms.     

Associations of common noncommunicable medical conditions and chronic diseases with chronotype in a population-based health examination study

Chronotype is an emerging predictor of health and longevity, and understanding its influence on chronic diseases is important for constructing conceptual models of long-term pathways to health. We assessed the associations of chronotype with health status in the general Finnish adult population. Our population-based data were derived from the National FINRISK 2012 study and consisted of 4414 participants, aged 25–74?years, living in Finland. As part of their health examination, participants were asked about their circadian preference to the daily activities (morningness–eveningness) and a diagnosis or treatment for a set of common noncommunicable medical conditions and chronic diseases during the past 12?months. We found that there were 1935 (43.8%) morning types (MTs) and 595 (13.5%) evening types (ETs) and that 1884 (42.7%) were intermediates. As compared with the MTs, the ETs had significantly greater odds for depression (OR = 2.44, 95% CI = 1.52–3.90, p < 0.001) and other mental disorders (OR = 5.18, 95% CI = 2.32–11.52, p < 0.001). The odds were also increased for gallstones, and chronic obstructive pulmonary disease, but these did not remain significant after controlling for multiple testing. Responses to the single-item subjective estimation on the chronotype yielded the association of the definitely evening type of persons with the diagnosis or treatment of cardiac insufficiency (OR = 1.99, 95% CI = 1.02–3.88, p = 0.044) that was corroborated as the greater the eveningness score was, the more common the diagnosis or treatment of cardiac insufficiency was (β = 0.92, 95% CI = 0.85–0.98, p = 0.013). This exploratory study adds further support to the role of evening chronotype in chronic disease risk, albeit underlying mechanisms remain to be elucidated.     

Circadian Preference and Thinking Styles: Implications for School Achievement

Research has shown that thinking styles could have an influence on academic achievement. Previous studies have described that evening types are usually right-thinkers who tend to be creative and intuitive, whereas morning types tend to be left-thinkers who prefer verbal and analytic strategies in processing information. However, these studies have been realized among undergraduates, who have more freedom to choose their time schedules according to their circadian preference than adolescents or adult workers. On other hand, the relationship between thinking styles and circadian preference has not been analyzed considering school achievement. The present study aims (1) to investigate the relationship between circadian preference, that is, behavioral differences in circadian rhythmic expression, and thinking styles, referring to the preference toward information processing typical of the right versus the left cerebral hemisphere; and (2) to test the implications for self-reported school achievement. A sample of 1134 preadolescents and adolescents (581 girls; mean?±?SD age: 12.1?±?1.47, range: 10–14?yrs) completed the Morningness-Eveningness Scale for Children (MESC) as measure of circadian preference (morning, neither, or evening types), the Hemispheric Preference Test (HPT), conceived as a tool to measure thinking styles (right-, balanced-, and left-thinkers), and self-reported school achievement. Results indicated a greater percentage of left-thinkers among morning types and a greater percentage of right-thinkers among evening types. No differences were found among balanced-thinkers and neither types. Morning types and left-thinkers reported the highest subjective level of achievement, followed by evening types and left-thinkers, and morning types and right-thinkers. Evening types and right-thinkers reported the lowest subjective level of achievement. Finally, multivariate regression analysis indicated that age, left hemisphere and morning preferences accounted for 14.2% of total variance on self-reported achievement.     

miR-499 rs3746444 polymorphism is associated with cancer development among Asians and related to breast cancer susceptibility

To derive a more precise estimation of the relationship between miR-499 rs3746444 polymorphism (A>G) and cancer risk, a meta-analysis was performed. A total of 9 studies including 6,077 cases and 7,199 controls were involved in this meta-analysis. Overall, no significantly elevated cancer risk was associated with miR-499 G allele when all studies were pooled into the meta-analysis (AG vs. AA: OR?=?1.14, 95?% CI?=?0.98–1.32; GG vs. AA: OR?=?1.12, 95?% CI?=?0.95–1.33; dominant model: OR?=?1.13, 95?% CI?=?0.99–1.29; recessive model: OR?=?1.05, 95?% CI?=?0.83–1.33). In the subgroup analysis by ethnicity, significantly increased risk was only found for Asians (dominant model: OR?=?1.22, 95?% CI?=?1.02–1.46). When stratified by study design, no statistically significantly elevated risks were found in hospital-based studies or population-based studies. In the subgroup analysis by cancer type, significant cancer risk change was only found for breast cancer when miR-499 G allele was included (dominant model: OR?=?1.13, 95?% CI?=?1.01–1.26). In conclusion, this meta-analysis suggests that the miR-499 rs3746444 polymorphism (A>G) is a low-penetrant risk factor for cancer development among Asians and may contribute to breast cancer susceptibility.     

Evidence for a relationship between chronotype and reproductive function in women

There is evidence for the reciprocal interaction between circadian oscillation and reproduction, and disruption of circadian rhythms has been associated with impaired menstrual functions and reduced fertility in women. However, only little information is available on the relationship between reproduction and chronotype. The aim of the present study is to better assess this relationship. The participants (aged 25 to 74?yrs) were selected randomly from the Finnish Population Information System. The data from 2672 female participants of the National FINRISK Survey 2007 were analyzed to test the associations between chronotype (morning, intermediate, or evening) and reproductive features. Of the participants, 139 (5.6%) were evening, 1217 (48.7%) intermediate, and 1145 (45.8%) morning chronotypes. Among the participants aged 25 to 54?yrs, the duration of menstrual cycle was longer among evening chronotypes (28.8?±?4.4?d) than among morning (27.7?±?2.6?d; p?<?0.01) and intermediate (27.8?±?3.3?d; p?=?0.05) chronotypes. Significant correlations were found between the higher morningness-eveningness scores (the more of morning chronotype) and the shorter durations of menstrual bleeding, both in the whole sample (p?<?0.001) and after limiting the analyses to women younger than 55?yrs (p?<?0.05). In multivariable analyses on the whole sample, as compared with morning chronotypes, intermediate chronotypes had a significantly longer duration of menstrual bleeding (B?=?0.160, 95% confidence interval [CI]?=?0.044 to 0.276; p?<?0.01) as well as a higher odds for difficulties in getting pregnant (odds ratio [OR]?=?1.464, 95% CI?=?1.118 to 1.917; p?<?0.01). Our findings suggest that chronotype is related to the reproductive function in women.     

Evening chronotype is associated with poor cardiovascular health and adverse health behaviors in a diverse population of women

ABSTRACT

Chronotype reflects time of day preferences for performing daily activities. Previous research within Asian and European cohorts indicates evening chronotype is associated with elevated cardiometabolic risk. However, evidence is limited from population-based US cohorts, particularly among women in whom evening chronotype prevalence may become higher after middle-age, coinciding with life stages associated with higher cardiovascular disease (CVD) risk. This cross-sectional study evaluated associations of chronotype with overall cardiovascular health (CVH), health behaviors, and cardiometabolic risk factors among 506 women (mean age = 37 ± 16y, 62% racial/ethnic minority) in the American Heart Association (AHA)’s Go Red for Women Strategically-Focused Research Network cohort at Columbia University (New York City, NY, USA). Chronotype was assessed using the validated Morningness-Eveningness Questionnaire (MEQ) and categorized as “evening”, “intermediate”, and “morning” chronotypes. Health behaviors (diet, physical activity, and sleep) were assessed using validated questionnaires. Anthropometrics, clinical blood pressure, and blood biomarkers were assessed at the clinic visit. CVH was evaluated using the AHA Life’s Simple 7 (LS7) metrics; LS7 scores of 0–8 and 9–14 were considered indicative of poor and moderate-to-high CVH, respectively. Linear and logistic regression models adjusted for age, race/ethnicity, education, health insurance, and menopausal status were used to examine associations of MEQ scores and chronotype categories with overall CVH, clinical cardiometabolic risk factors, and health behaviors. Overall, 13% of women identified as evening chronotypes, while 55% and 32% reported being intermediate and morning types. In linear models, higher MEQ scores were associated with higher AHA LS7 scores (β(SE) = 0.02(0.01); p = .014), indicative of more favorable CVH, and with health behaviors not included in the LS7. Higher MEQ scores were also associated with lower Pittsburgh Sleep Quality Index, i.e. better sleep quality, (β(SE) = ?0.07(0.02), p < .0001), lower insomnia severity (β(SE) = ?0.14(0.01), p < .0001), shorter time to fall asleep (β(SE) = ?0.28(0.14), p = .044), and less sedentary time (β(SE) = ?0.11(0.03), p = .001). In logistic regression models, evening chronotype, compared to intermediate/morning type, was associated with higher odds of having poor CVH (OR(95%CI):2.41(1.20–4.85)), not meeting AHA diet (OR(95%CI):2.89(1.59–5.23)) and physical activity guidelines (OR(95%CI):1.78(1.03–3.07)), and having short sleep (OR(95%CI):2.15(1.24–3.73)) or insomnia (OR(95%CI):2.69(1.53–4.75)). The evening type compared to morning type was also associated with being a current smoker (OR(95%CI):2.14(1.02–4.52)) and having poor sleep quality (OR(95%CI:2.35(1.27–4.37)) and long sleep onset latency (OR(95%CI:1.89(1.00–3.56)). In our cohort of women, evening chronotype was related to poor CVH, likely driven by its influence on health behaviors. These findings, although warranting confirmation prospectively in other populations, suggest chronotype is an important factor to consider and possibly target when designing lifestyle interventions for CVD prevention.     

Evening typology and morning tiredness associates with low leisure time physical activity and high sitting

Circadian typology is a latent trait that is usually assessed with scoring on a series of questions thought to represent the construct. But, in the classification, most people fall into the intermediate type, i.e. neither a definite morning nor an evening type, but still showing stronger preference towards either end of the continuum. Our aim was to operationalize chronotype using latent class analysis (LCA) for a 6-item scale derived from the original Horne–Östberg Morningness–Eveningness Questionnaire to compare and understand characteristics of chronotype in a population-based sample of adults in Finland. A total of 4904 men and women aged 25–74 years were included. We also analyzed the associations of chronotypes with physical activity (PA) and sitting. We found five latent chronotype groups including “rested more-evening type” (28%), “rested more-morning type” (24%), “morning type” (23%), “tired more-evening type” (17%) and “evening type” (8%) groups. Operationalization of chronotype by LCA suggests that morning alertness is an important feature differentiating chronotypes. Further, the “evening type” and the “tired, more-evening type” had higher odds for none to very low as well as low PA, as compared to “morning type”. In addition, “evening type” was associated with higher odds for more time spent sitting, as compared to “morning type”. Our findings indicate that it is important to assess sleep schedules and morning tiredness, which then could be targeted as a potential mediating factor for health behaviors, in particular, PA and health status.     

Genetic association between IL-27 rs153109 polymorphism and cancer risk in Chinese population: a meta-analysis

IL-27 plays an important role in anti-cancer activity. The -964A/G polymorphism in IL-27 gene has been implicated in susceptibility to cancer, but the results were conflicting. The aim of this study was to assess the association between this polymorphism and cancer risk. Pubmed and Wanfang database were searched for all publications concerning IL-27 -964A/G polymorphism and cancer risk. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. Statistical analysis was performed using Stata 11.0 software. A total of eight case–control studies including 2044 cancer cases and 2197 controls were identified. Overall, significant association between IL-27 -964A/G polymorphism and cancer risk was observed (GG versus AA: OR?=?1.26, 95% CI?=?1.03–1.52; GG versus AG?+?AA: OR?=?1.20, 95% CI?=?1.00–1.44). In subgroup analysis based on cancer type, significant association was found in colorectal cancer (GG versus AA: OR?=?1.55, 95% CI?=?1.07–2.27; AG versus AA: OR?=?1.31, 95% CI?=?1.02–1.67). The current meta-analysis suggests that IL-27 -964A/G polymorphism might enhance cancer risk. However, large-scale and well-designed studies are still needed to confirm the result of our meta-analysis. The association of IL-27 polymorphism with colorectal cancer may provide insight for future therapies.     

The association between chronotype and perceived academic stress to depression in medical students

Depression is a multifactorial illness that is highly prevalent among medical students (MS). Chronotypes, which reflect circadian preference in humans, as well as academic stress have been associated with depression in different populations. However, it is not known how chronotype and stress might alone or in combination, associate with depression in MS. Thus, we aimed to evaluate the association between stress, chronotype and depression in MS. In a cross-sectional study, we evaluated a total of 1068 medical students from a public Medical School in Mexico City. The Patient Health Questionnaire-9 (PHQ-9) was used to evaluate depressive symptom severity and the presence of a current depressive episode with a cutoff score of 10 or higher. The Morning-Evening Questionnaire (MEQ) was used to establish chronotype and the Academic Stress Inventory was used to measure perceived academic stress (PAS). We observed that depressive symptom severity was higher in non-morning chronotypes and moderate/severe PAS groups. A factorial ANOVA showed an association between PAS groups and depressive symptom severity. Linear regression showed an association between depressive symptom severity and variables such as PAS scores (p = 0.001), family history of depression (p = 0.001), gender (p = 0.001) and academic year (p = 0.029). Logistic regression analysis showed that evening chronotype (OR: 2.3, 95% CI: 1.2–4.3, p = 0.01) and severe PAS (OR: 4.4, 95% CI: 2.8–7.0, p = 0.0001) were associated with depression. Further, MS with the combination of severe PAS and morning (OR: 5.9, 95% CI: 1.6–22.2, p = 0.01), intermediate (OR: 7.5, 95% CI: 2.3–24.4, p = 0.001) or evening (OR: 10.6, 95% CI: 2.8–40.0, p = 0.001) chronotypes showed a greater association with depression than any PAS or chronotype group alone. Being female, perceiving restricted or limited economic resources, having severe scores of academic stress, and evening chronotype were associated with an increased probability to suffer a current depressive episode. Collectively, these results show that chronotype and PAS are factors associated with depression in MS, and when combined promote this association. Our results might aid in early identification of MS susceptible to depression. Future research could focus on the implementation of simple, low cost preventive strategies, such as chronotype-oriented academic schedules.     

Chronotype and energy intake timing in relation to changes in anthropometrics: a 7-year follow-up study in adults

Individuals with a later preference for the daily activities (evening types) tend to have unhealthier behaviors, which could increase their risk for obesity when compared those with an earlier preference (morning types). Furthermore, later food intake timing, another behavior more characteristic of evening types, has been associated with obesity. However, chronotype differences in the long-term weight change and the role of chronotype in the association between energy intake timing and obesity risk are not clear. To study this we first examined the independent associations of chronotype and energy intake timing with anthropometric changes and then whether chronotype modified the association between energy intake timing and obesity risk. Our data included 1097 Finns from DILGOM (DIetary Lifestyle and Genetic Determinants of Obesity and Metabolic syndrome) 2007 (baseline) and 2014 (follow-up) and from Findiet 2007. Chronotype was assessed with a shortened version of Horne and Östberg’s morningness–eveningness questionnaire. Energy intake timing (as percentages of the total energy intake in the morning/evening) was assessed with 48-h dietary recalls. Weight, body mass index (BMI), and waist circumference were based on measured and self-reported values. Analysis of co-variance and multivariable logistic regression models were used for statistical analyses. Evening typed women had greater weight gain (+ 2.3 kg vs. + 0.3 kg, P = 0.016) and increase in BMI (0.7 kg/m² vs. ?0.1 kg/m², P = 0.024) than morning typed women. After excluding participants with depression, these associations attenuated to non-significant. Compared to participants whose energy intake was proportionally lowest during evening, those with proportionally highest energy intake during evening were more likely with obesity (BMI≥ 30 kg/m²) after follow-up (OR 1.97, 95% CI 1.21–3.21, Ptrend = 0.042). Participants’ chronotype did not modify this association (Pinteract = 0.95). In conclusion, our findings indicated that evening energy intake may play a role in obesity regardless of the chronotype. Furthermore, evening typed women were more prone to increases in their anthropometrics, which seem to be at least partly explained by depression. Further studies of this topic are warranted.     

Interleukin-12B rs3212227 polymorphism and cancer risk: a meta-analysis

IL-12 plays a very important role in the development and progress of cancer. IL-12B rs3212227 polymorphism has been reported and many studies have focused on the role of this polymorphism in various cancers. However, the association between IL-12B rs3212227 polymorphism and cancer risk remains controversial. Therefore, we performed a systematic meta-analysis to estimate the overall cancer risk associated with this gene polymorphism and to quantify any potential between-study heterogeneity. PubMed and Embase databases were searched for case–control studies published up to April 1, 2012 that investigated IL-12B rs3212227 polymorphism and cancer risk. Odds ratios (OR) with 95?% confidence intervals (95?% CI) were used to access the strength of this association. Heterogeneity among articles and publication bias were also verified. Ten studies with 2,954 cancer patients and 3,276 healthy controls were included. This meta-analysis showed that there was a significant association between IL-12B rs3212227 polymorphism and overall cancer risk (CC/AC vs AA: OR?=?1.32, 95?% CI?=?1.06–1.63). When stratified by cancer type, we found a significant increased risk in cervical and nasopharyngeal cancer (OR?=?1.34, 95?% CI?=?1.04–1.73; OR?=?2.03, 95?% CI?=?1.57–2.63, respectively). In the stratified analysis, we also observed a similar association in population-based studies (OR?=?1.34, 95?% CI?=?1.00–1.80), Asian populations (OR?=?1.33, 95 % CI?=?1.06–1.67) and European populations (OR?=?1.54, 95 % CI?=?1.04–2.28). According to the results of our meta-analysis, IL-12B rs3212227 polymorphism probably is associated with a high risk of cancer.     

Zeitgebers and their association with rest-activity patterns

Zeitgebers such as light, eating and physical activity provide input to the circadian clock. Chronic circadian misalignment is associated with significant adverse health effects. An improved understanding of the impact of the timing of zeitgebers on the stability of 24-hour rest-activity rhythm in free-living settings may identify behavioural and environmental intervention targets. A total of 133 healthy adults, aged 21–60 years, wore a wrist actigraph for 7 consecutive days. We applied a non-parametric analysis to activity counts to derive rest-activity patterns. We administered a questionnaire through a smartphone app to collect self-reported timing of light exposure, eating episodes and physical activity. To assess the relationship between timing exposures (first and last exposure to outdoor light, first exposure to indoor light, last eating episode, first eating episode, morning physical activity proportion, evening physical activity proportion) and rest-activity or sleep outcomes (bedtimes, total sleep time, inter-daily stability, intra-daily variability, L5 and M10 midpoint), we first calculated Spearman correlations, using the false discovery rate method to control for multiple comparisons. From those significant associations, we then fit regression models adjusting for age, sex, race, household income, education level, study site, body mass index, as well as physical activity. Finally, we tested for interaction between chronotype and each timing-related exposure and stratified the analysis by morning type. All zeitgebers, except for evening physical activity proportion, were correlated with at least four of the seven sleep and rest-activity outcomes. In adjusted analysis, later timing of first (after 6:30 to 7:45 AM versus earlier) and last exposure to indoor light (after 11:00 PM versus earlier) and first (after 7:45–9:45 AM versus earlier) and last eating episode (after 8:00–09:00 PM versus earlier) were associated with a shift of 0.60–1.39 hours to later bedtimes, M10 and L5 midpoints (i.e. timing of peak activities or inactivities). Later timing of first exposure to outdoor light (after 09:30 AM versus earlier) was also associated with 0.51 (95% CI: 0.19 to 0.83) hours longer total sleep time. Higher morning physical activity proportion (> 33%) was associated with 0.95 (95% CI: ?1.38 to ?0.53) hours earlier in-bed time and 0.69 (95% CI: ?1.14 to ?0.24) hours earlier out-of-bed time, 0.92 (95% CI: ?1.41 to ?0.42) hours earlier M10 and 0.96 (95% CI: ?1.42 to ?0.49) min earlier L5 midpoint. The results did not change substantially with further adjustment for total activity. There was a significant interaction between morning chronotype and first eating episode with rest-activity patterns (p < 0.05), with first eating episode associating with timing of activities only in non-morning type adults. Timing of zeitgebers was associated with sleep and rest-activity patterns, including bedtimes, L5 and M10 midpoint. Future research should evaluate the impact of manipulating zeitgebers on both circadian rhythms and health outcomes.     

Associations of chronotype with social jetlag and behavioral problems in preschool children

The timing, duration, and intensity of sleep are determined by the interaction between a sleep-wake-dependent homeostatic process and a sleep-wake-independent, intrinsic, clock-like circadian process. Chronotype represents individual differences in diurnal preferences, which are not only genetically determined but also influenced by social and environmental factors. Thus, the discrepancy between biological and social clocks, so-called “social jetlag”, occurs. Chronotype, social jetlag, and the links between chronotype and behavioral problems are well documented in adults and adolescents. However, such studies on young children are limited. We conducted a survey of sleep and health for preschool children attending kindergarten or childcare centers in Wako, Okayama and Kurashiki cities, Japan, between May and July 2012. A total of 654 children aged 4–6 years (342 boys and 312 girls, with an average age of 4.7 years) were assessed using the Children’s ChronoType Questionnaire and the Strength and Difficulties Questionnaire. Morning (M)-type, neither (N)-type and evening (E)-type accounted for 36.2%, 54.0% and 9.8% of the participants, respectively. The weekday-to-weekend differences in midsleep time – originally proposed as the concept of social jetlag – were 11, 25 and 35?min for M-, N- and E-types, respectively. There was a negative correlation between chronotype and sleep period during weekdays (p?<?0.001) and a positive correlation on weekends (p?<?0.001). The weekday-to-weekend difference in sleep period was 0.5?h for E-types, whereas there was no difference for M-types. Binomial logistic regression analyses were used to examine the links between chronotype and behavioral problems, adjusted for participants’ sex, age, childcare programs and locations. Chronotype was significantly associated with hyperactivity/inattention: N-type (adjusted OR?=?1.74, 95% CI?=?1.03–2.95, p?<?0.05) and E-type (adjusted OR?=?2.47, 95% CI?=?1.18–5.20, p?<?0.05). E-type was significantly associated with conduct problems (adjusted OR?=?2.11, 95% CI?=?1.03–4.31, p?<?0.05) and peer problems (adjusted OR?=?2.75, 95% CI?=?1.18–6.44, p?<?0.05). The results suggest that E-type children are vulnerable to higher social jetlag and more behavioral problems. The immature adjustment function of their endogenous circadian pacemakers may not be able to correct a small but significant social jetlag to synchronize with their social clocks. Furthermore, guidance based on chronobiological evidence is required for parents, teachers and health professionals to help children achieve optimal sleep and reduce behavioral problems.     

Effect of circadian rhythm type on serum lipid levels in shift workers: A 5-year cohort study

We investigated how differences in circadian rhythm type affect the health of workers engaged in shift work. Employees, who were newly hired in a steel company between 2007 and 2011, received the Morningness–Eveningness Questionnaire (MEQ) survey. The target participants were 153 male shift workers who were not being treated with any antihyperlipidemic drugs and underwent periodic physical examinations including blood tests at least twice. According to the score of the MEQ at the time of joining the company, we classified the subjects into five types. Longitudinal changes in serum lipid level were estimated among the circadian rhythm types adjusted for age, BMI, and other covariates using a linear mixed model. The regression coefficient of total cholesterol level in the “definitely and moderately morning” group was ?17.83 (95% confidence interval (CI): ?33.42 to ?2.23), and in the “intermediate ‘group’ was ?16.84 [95% CI: ?30.40 to ?3.28], compared to the moderate evening type.” The total cholesterol level was higher in the moderately evening type than in any of the other groups. Between the Morningness–Eveningness (ME) type and Low-density lipoprotein (LDL) cholesterol levels, compared with the “moderately evening type” group, the regression coefficient in the “intermediate type” group was ?16.08 (95% CI: ?28.79 to ?3.37), and in the “definitely and moderately morning type” group was ?17.50 [95% CI: ?32.11 to ?2.88]. The “moderately evening type” group had a higher LDL cholesterol level than any of the other groups. Evening-type circadian rhythm type shift workers are more prone to elevated serum lipid levels.     

Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study

Morning-preference chronotype has been found to be protective against breast and prostate cancer. Sex hormones have been implicated in relation to chronotype and the development of both cancers. This study aimed to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer using a Mendelian Randomization (MR) framework. Genetic variants associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin, and oestradiol) (p<5×10⁻⁸) were obtained from published genome-wide association studies (n≤244,207 females and n≤205,527 males). These variants were used to investigate causal relationships with breast (nCases/nControls = 133,384/113,789) and prostate (nCases/nControls = 79,148/61,106) cancer using univariable, bidirectional and multivariable MR. In females, we found evidence for: I) Reduced risk of breast cancer per category increase in morning-preference (OR = 0.93, 95% CI:0. 88, 1.00); II) Increased risk of breast cancer per SD increase in bioavailable testosterone (OR = 1.10, 95% CI: 1.01, 1.19) and total testosterone (OR = 1.15, 95% CI:1.07, 1.23); III) Bidirectional effects between morning-preference and both bioavailable and total testosterone (e.g. mean SD difference in bioavailable testosterone = -0.08, 95% CI:-0.12, -0.05 per category increase in morning-preference vs difference in morning-preference category = -0.04, 95% CI: -0.08, 0.00 per SD increase in bioavailable testosterone). In males, we found evidence for: I) Reduced risk of prostate cancer per category increase in morning-preference (OR = 0.90, 95% CI: 0.83, 0.97) and II) Increased risk of prostate cancer per SD increase in bioavailable testosterone (OR = 1.22, 95% CI: 1.08, 1.37). No bidirectional effects were found between morning-preference and testosterone in males. While testosterone levels were causally implicated with both chronotype and cancer, there was inconsistent evidence for testosterone as a mediator of the relationship. The protective effect of morning-preference on both breast and prostate cancer is clinically interesting, although it may be difficult to effectively modify chronotype. Further studies are needed to investigate other potentially modifiable intermediates.     

Chronotype and sleep duration are associated with stimulant consumption and BMI among Chinese undergraduates

The study sought to identify the association between stimulant consumption and social jetlag, chronotype as well as sleep duration among undergraduate students. A cross-sectional survey was conducted in the university town in Chongqing, China. Data were collected on 977 participants, age 20.06 (SD = 1.25) years old, using the Munich Chronotype Questionnaire (MCTQ) to measure social jetlag, chronotype and average sleep duration. A self-reported questionnaire was used to collect the information: BMI, demographic data, outdoor activity time, smoking status, alcohol consumption, coffee consumption and sugar-sweetened beverage consumption. The positive significant association was found between late chronotype and alcohol consumption (OR = 1.26, 95% CI [1.05–1.52]), being a current smoker (OR = 1.62, 95% CI [1.26–2.07]) and sugar-sweetened beverage consumption (OR = 1.42, 95% CI [1.17–1.72]). Average sleep duration was negatively associated with BMI (OR = 0.84, 95% CI [0.71–0.98]). Social jetlag did not find any association between stimulant consumption and BMI in the adjusted model. The results showed that Chinese undergraduate students had a negative significant association between average sleep duration and BMI, and late chronotype might affect the stimulant consumption among the group. This study may provide some implications for health management of obesity among undergraduate students in China.