Diabetes,metabolic syndrome and prostate cancer risk: Results from the EPICAP case-control study

BackgroundDiabetes may be associated with decreased prostate cancer (PCa) risk. However, previous studies have not always accounted for time since diabetes diagnosis or antidiabetic drug use. Futhermore, the role of metabolic syndrome (MetS) in PCa risk is still debated. We investigated the role of diabetes and MetS in PCa risk based on data from the Epidemiological study of PCa (EPICAP).MethodsEPICAP is a population-based case-control study that included 819 incident PCa cases in 2012–2013 and 879 controls frequency matched by age. MetS was characterized according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Logistic regression models adjusted for age, family history of PCa and ethnicity, were used to assess odds ratios (ORs) and their 95%conficence intervals (CIs) for the associations between diabetes, MetS and PCa risk.ResultsWhereas we did not observed an association between diabetes and PCa, a decreased risk of PCa has been highlighted with an increasing treated diabetes duration (p-trend=0.008). No association has been observed between MetS, the number of MetS criteria and the risk of PCa. However, we suggested that NSAIDs use could modify the association between MetS and PCa risk.ConclusionOur results suggest an inverse association between the duration of diabetes and PCa risk. The role of metabolic factors, such as MetS and its components, in PCa risk remains unclear and requires further investigations.     

Common variants in the obesity-associated genes FTO and MC4R are not associated with risk of colorectal cancer

BackgroundObesity is a convincing risk factor for colorectal cancer. Genetic variants in or near FTO and MC4R are consistently associated with body mass index and other body size measures, but whether they are also associated with colorectal cancer risk is unclear.MethodsIn the discovery stage, we tested associations of 677 FTO and 323 MC4R single nucleotide polymorphisms (SNPs) 100 kb upstream and 300 kb downstream from each respective locus with risk of colorectal cancer in data from the Colon Cancer Family Registry (CCFR: 1960 cases; 1777 controls). Next, all SNPs that were nominally statistically significant (p < 0.05) in the discovery stage were included in replication analyses in data from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO: 9716 cases; 9844 controls).ResultsIn the discovery stage, 43 FTO variants and 18 MC4R variants were associated with colorectal cancer risk (p < 0.05). No SNPs remained statistically significant in the replication analysis after accounting for multiple comparisons.ConclusionWe found no evidence that individual variants in or near the obesity-related genes FTO and MC4R are associated with risk of colorectal cancer.     

Shift work,circadian gene variants and risk of breast cancer

Circadian (clock) genes have been linked with several functions relevant to cancer, and epidemiologic research has suggested relationships with breast cancer risk for variants in NPAS2, CLOCK, CRY2 and TIMELESS. Increased breast cancer risk has also been observed among shift workers, suggesting potential interactions in relationships of circadian genes with breast cancer. Relationships with breast cancer of 100 SNPs in 14 clock-related genes, as well as potential interactions with shift work history, were investigated in a case–control study (1042 cases, 1051 controls). Odds ratios in an additive genetic model for European-ancestry participants (645 cases, 806 controls) were calculated, using a two-step correction for multiple testing: within each gene through permutation testing (10,000 permutations), and correcting for the false discovery rate across genes. Interactions of genotypes with ethnicity and shift work (<2 years vs ≥2 years) were evaluated individually. Following permutation analysis, two SNPs (rs3816360 in ARNTL and rs11113179 in CRY1) displayed significant associations with breast cancer and one SNP (rs3027188 in PER1) was marginally significant; however, none were significant following adjustment for the false discovery rate. No significant interaction with shift work history was detected. If shift work causes circadian disruption, this was not reflected in associations between clock gene variants and breast cancer risk in this study. Larger studies are needed to assess interactions with longer durations (>30 years) of shift work that have been associated with breast cancer.     

The circadian disruption of night work alters gut microbiota consistent with elevated risk for future metabolic and gastrointestinal pathology

ABSTRACT

Day and night cycles are the most important cue for the central clock of human beings, and they are also important for the gut clock. The aim of the study is to determine the differences in the gut microbiota of rotational shift workers when working the day versus night shift. Fecal samples and other data were collected from 10 volunteer male security officers after 4 weeks of day shift work (07:00–15:00 h) and also after 2 weeks of night shift work (23:00–07:00 h). In total, 20 stool samples were collected for analysis of gut microbiota (10 subjects x 2 work shifts) and stored at ?80°C until analysis by 16 S rRNA sequencing. The relative abundances of Bacteroidetes were reduced and those of Actinobacteria and Firmicutes increased when working the night compared to day shift. Faecalibacterium abundance was found to be a biomarker of the day shift work. Dorea longicatena and Dorea formicigenerans were significantly more abundant in individuals when working the night shift. Rotational day and night shift work causes circadian rhythm disturbance with an associated alteration in the abundances of gut microbiota, leading to the concern that such induced alteration of gut microbiota may at least partially contribute to an increased risk of future metabolic syndrome and gastrointestinal pathology.     

Trajectories of sleepiness and insomnia symptoms in Norwegian nurses with and without night work and rotational work

Numerous cross-sectional studies report high prevalence rates of sleepiness and insomnia in shift workers, but few longitudinal studies exist. We investigated trajectories of sleepiness and insomnia symptoms in a sample of Norwegian nurses across four measurements, spanning a total of four years (sleepiness) and five years (insomnia). The participants completed the Epworth Sleepiness Scale and the Bergen Insomnia Scale at each measurement instance. Latent growth curve models were used to analyse the data. Separate models examined night work (night work, entering and leaving night work) and rotational work (rotational work, entering and leaving rotational work) as predictors for trajectories of sleepiness and insomnia symptoms, respectively. Baseline values of sleepiness and insomnia were higher among rotational shift workers than among workers with fixed shifts (day or night). The results showed that night work throughout the period and entering night work during the period were not associated with different trajectories of sleepiness or insomnia symptoms, compared to not having night work. The same results were found for rotational work and entering rotational work, compared to not having rotational work. Leaving night work and leaving rotational work were associated with a decrease in sleepiness and insomnia symptoms, compared to staying in such work.     

Rotating night shift work and nutrition of nurses and midwives

Previous research points to some inappropriate nutritional habits among nurses working night shifts. However, the knowledge of specific nutritional components of their diet has been limited. In the present study, we aimed to investigate the association between rotating night shifts of nurses and midwives and their usual dietary intake of energy and nutrients.

A cross-sectional study was conducted among 522 Polish nurses and midwives: 251 working rotating night shifts (i.e. working night shift followed by a day off on a subsequent day) and 271 day workers. Polish adaptation of the Food Frequency Questionnaire, regarding 151 food items, was used to assess the usual dietary energy and nutrient intake. Data on occupational history and potential confounders were collected via face-to-face interviews. Body weight, height, waist and hip circumference were measured. Linear regression models: univariate (crude) and multivariate (adjusted) were run, with the nutrient intake as dependent variables, night work characteristics, and important confounders.

Among nurses and midwives working rotating night shifts, a significantly higher adjusted mean intake was found for the total energy (2005 kcal vs 1850 kcal) and total fatty acids (77.9 g vs 70.4 g) when compared to day workers, as well as for cholesterol (277 mg vs 258 mg), carbohydrates (266 g vs 244 g) and sucrose (55.8 g vs 48.6 g). Night shift work duration was inversely related to the consumption of calcium, phosphorus, vitamin A, vitamin C and % energy from proteins. The higher energy consumption may contribute to increase risk of overweight and obesity among nurses working night shifts.     

The effects of exposure to night shift work on liver function: A cross-sectional study with emphasis of alkaline phosphatase enzyme

ABSTRACT

Background: Previous studies have demonstrated that shift work can be significantly associated with adverse effects on liver function. However, the association between shift work and alkaline phosphatase (ALP) enzyme as a well-known biomarker of liver disease has been undefined. Methods: This cross-sectional study was conducted on a total number of 6,475 eligible oil refinery workers. According to shift work schedules, the participants divided to the following groups: 12-hr rotating night (n = 2,630) and 12-hr fixed day (n = 3845). The Spearman’s correlation and logistic regression were applied to assess the association between shift work and ALP. Results: We found significantly higher levels of ALP in 12-hr rotating night compared to 12-hr fixed-day shift work groups (196.2 ± 52.1 versus 191.5 ± 53.4). According to quartile (Q) logistic regression adjusted by significant variables between study group (age, body mass index, fasting blood sugar, and total cholesterol), the odds ratio and 95% confidence interval of high (Q2–<Q3 versus <Q1) and severe (≥Q3 versus <Q1) levels of ALP in 12-hr rotating night group in comparison to 12-hr fixed-day group were estimated as 1.26 (1.08–1.45) and 1.26 (1.09–1.45), respectively. Conclusions: This study indicated that 12-hr rotating night shift work may be associated with higher levels of ALP. More studies are needed to confirm our findings.     

Obesity,physical activity and cancer risks: Results from the Cancer,Lifestyle and Evaluation of Risk Study (CLEAR)

IntroductionPhysical activity (PA) has been associated with lower risk of cardiovascular diseases, but the evidence linking PA with lower cancer risk is inconclusive. We examined the independent and interactive effects of PA and obesity using body mass index (BMI) as a proxy for obesity, on the risk of developing prostate (PC), postmenopausal breast (BC), colorectal (CRC), ovarian (OC) and uterine (UC) cancers.MethodsWe estimated odds ratios (OR) and 95% confidence intervals (CI), adjusting for cancer specific confounders, in 6831 self-reported cancer cases and 1992 self-reported cancer-free controls from the Cancer Lifestyle and Evaluation of Risk Study, using unconditional logistic regression.ResultsFor women, BMI was positively associated with UC risk; specifically, obese women (BMI ≥30 kg/m²) had nearly twice the risk of developing UC compared to women with healthy-BMI-range (<25 kg/m²) (OR = 1.99;CI:1.31–3.03). For men, BMI was also positively associated with the risk of developing any cancer type, CRC and PC. In particular, obese men had 37% (OR = 1.37;CI:1.11–1.70), 113% (OR = 2.13;CI:1.55–2.91) and 51% (OR = 1.51;CI:1.17-1.94) higher risks of developing any cancer, CRC and PC respectively, when compared to men with healthy-BMI-range (BMI<25 kg/m²).Among women, PA was inversely associated with the risks of CRC, UC and BC. In particular, the highest level of PA (versus nil activity) was associated with reduced risks of CRC (OR = 0.60;CI:0.44–0.84) and UC (OR = 0.47;CI:0.27–0.80). Reduced risks of BC were associated with low (OR = 0.66;CI:0.51–0.86) and moderate (OR = 0.72;CI:0.57–0.91) levels of PA. There was no association between PA levels and cancer risks for men.We found no evidence of an interaction between BMI and PA in the CLEAR study.ConclusionThese findings suggest that PA and obesity are independent cancer risk factors.     

Changes in the diurnal rhythms of cortisol,melatonin, and testosterone after 2, 4, and 7 consecutive night shifts in male police officers

Night work is associated with a large range of acute health problems and possibly also health consequences in the long run. Yet, only very few field studies specifically investigate the effects of consecutive night shift on key physiological regulatory systems. In this field study, we investigated the effects of consecutive night shifts on three hormones, melatonin, cortisol, and testosterone, among police officers at work. More specifically, the aim was to investigate how the diurnal rhythms of melatonin, cortisol, and testosterone responded to two, four, and seven consecutive night shifts and a corresponding number of days for recovery. The study was part of the “In the Middle of the Night” project and included 73 male police officers from five different police districts. The participants were exposed to three intervention conditions: “2+2”: two consecutive night shifts followed by two consecutive day recovery days; “4+4”: four consecutive night shifts followed by four consecutive recovery days; “7+7”: seven consecutive night shifts followed by seven consecutive recovery days. On the last day with night shift and the last recovery day in each intervention, the participants collected saliva samples every 4th hour when awake. The diurnal rhythms of melatonin, cortisol, and testosterone were all affected differently by an increasing number of consecutive night shifts: the amplitude of the melatonin rhythm was suppressed by 4.9% per day (95% CI 1.4–8.2% per day; p = 0.006). The diurnal rhythm of cortisol phase was delayed with an increasing number of night shifts by 33 min/day (95% CI 18–48 min per day; p ≤ 0.001), but did not show any changes in amplitude. For the diurnal rhythm of testosterone, there was no effect of the number of consecutive night shifts and the diurnal rhythm completely followed the sleep/wake cycle. We found that there were no differences in the rhythms of melatonin, cortisol, and testosterone after 2, 4, and 7 recovery days, respectively. In conclusion, we found signs of desynchronization in terms of suppressed amplitude of melatonin and phase delay of salivary cortisol as a consequence of the increasing number of consecutive night shifts among police officers at work. Lack of synchronization has been suggested as a possible mechanism linking night work to disease, but this remains to be determined.     

Polymorphisms in the folate-metabolizing genes MTR, MTRR, and CBS and breast cancer risk

Alterations in the nucleotide sequences of folate-metabolizing genes can increase the risk of malignant transformation. The aim of our study was to investigate the association of three single-nucleotide polymorphisms (SNPs) in the folate-metabolizing genes - A2756G MTR, A66G MTRR, and 844ins68 CBS - which have putative functional significance in breast cancer risk. The allele and genotype frequencies of the SNPs were determined in a case group (840 women with sporadic breast cancer) and a control group (770 women). No statistically significant association of studied SNPs with breast cancer was revealed. A meta-analysis, which included data obtained from the literature and the present research, did not reveal any statistically significant associations of these SNPs with breast cancer. The results obtained provide evidence that these SNPs are not involved in the development of breast cancer.     

Shift work parameters and disruption of diurnal cortisol production in female hospital employees

Shift work is associated with an increased risk of cardiovascular diseases (CVD). Disruption of cortisol production is a potential underlying mechanism. This study explored the associations of diurnal quantity and pattern of cortisol production in relation to (1) current shift work status (exclusive day versus rotating days and nights), (2) years of past shift work and (3) parameters of rotating shift work (timing, length and intensity). Female hospital employees (160 day workers and 168 rotating shift workers) from southeastern Ontario, Canada, participated in a cross-sectional study. Participants completed a baseline questionnaire and measures of body height, weight, and waist circumference were taken. Midstream urine samples were collected over two separate 24-hour periods to measure creatinine-adjusted cortisol. Total diurnal cortisol production and pattern were described with two measures of the area under the curve. The effect of shift work on cortisol was modeled using multivariable linear regression analyses. Cortisol production in day workers and shift workers on their day shift were similar; however, shift workers on the night shift had flatter diurnal cortisol curves and produced less cortisol. This suggests that night work is associated with an acute attenuation of cortisol production.     

Shift work tolerance and the importance of sleep quality: a study of police officers

The aim of this study was to examine how subjective shift work tolerance was related to general health variables, with the expectation of inter-individual differences in the nature of this relation. A total of 740 employees of the Dutch Police force completed a questionnaire, covering seven health-related domains: sleep quality, sleep duration, need for recovery, fatigue, physical health, mental health, and work–life balance. Based on subjective reports of shift work tolerance, participants were classified as intolerant, medium-tolerant, or tolerant workers. Analysis involved group comparisons, regression, and cluster analysis. Eighteen percentage of the shift workers were classified as intolerant. The intolerant and medium-tolerant workers expressed more severe complaints than the tolerant workers, for all seven health-related domains. Shift work tolerance was primarily related to sleep quality and subsequently to need for recovery, fatigue, and work–life balance. No indications were found for systematic inter-individual differences in the nature of this relationship. For all participants equally, the degree of shift work tolerance was related to the severity of health-related complaints. This study highlights the central role of sleep for tolerance to shift work and underlines the need for occupational medicine to take explicit account of sleep.     

Asthma,allergy and the risk of prostate cancer: Results from the Montreal PROtEuS study

BackgroundThe few previous studies examining the association between asthma or allergy and prostate cancer (PCa) risk were inconclusive. This study aimed to evaluate these associations, and to explore in details the possible influence of current versus former allergic condition, age at onset, time since onset, and duration of each allergic condition.MethodsDetailed information on self-reported asthma and allergy was collected in the context of a large population-based case–control study conducted in Montreal, Canada. Study subjects included 1936 cases, diagnosed between 2005 and 2009, and 1995 population controls. Unconditional multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, ancestry and familial history of prostate cancer.ResultsThe ORs were 1.11 (95% CI: 0.89–1.40) and 0.98 (95% CI: 0.84–1.14) for ever reporting of asthma and allergy, respectively. These ORs did not substantially vary according to status (former or current), age at onset, time since onset, and duration of each allergic condition. PCa screening was not associated with allergic diseases reporting.ConclusionsOverall, our findings are in line with the absence of an association between a history of asthma or allergy, and PCa risk.     

The effect of the Flemish breast cancer screening program on breast cancer-specific mortality: A case-referent study

BackgroundBreast cancer screening programs were introduced in many countries worldwide following randomized controlled trials in the 1980s showing a reduction in breast cancer-specific mortality. However, their effectiveness remains debated and estimates vary. A breast cancer screening program was introduced in 2001 in Flanders, Belgium where high levels of opportunistic screening practices are observed. The effectiveness of this program was estimated by measuring its effect on breast cancer-specific mortality.MethodsWe performed a case-referent study to investigate the effect of participation in the Flemish population-based mammography screening program (PMSP) on breast cancer-specific mortality from 2005 to 2017. A multiple logistic regression model assessed the association between breast cancer-specific death and screening program participation status in the four years prior to (pseudo)diagnosis (yes/no), with adjustment for potential confounders (individual socio-economic position and calendar year of diagnosis) and stratified for age. In addition, we performed different sensitivity analyses.ResultsWe identified 1571 cases and randomly selected 6284 referents. After adjustment, women who participated in PMSP had a 51 % lower risk of breast cancer-specific mortality compared to those who did not (adjusted odds ratio [aOR] =0.49, 95 % CI: 0.44–0.55). Sensitivity analyses did not markedly change the estimated associations. Correction for self-selection bias reduced the effect size, but the estimate remained significant.ConclusionOur results indicate that in a context of high opportunistic screening rates, participation in breast cancer screening program substantially reduces breast cancer-specific mortality. For policy, these results should be balanced against the potential harms of screening, including overdiagnosis and overtreatment.     

The relationship between night work,chronotype, and cardiometabolic risk factors in female hospital employees

Night work has emerged as a risk factor for many chronic diseases, including obesity, diabetes, and cardiovascular disease. While night work is linked to a number of cardiometabolic indices, few studies have explored how different parameters, such as cumulative night work and intensity of night work, may influence cardiometabolic risk. Fewer studies have also explored the relationship while considering chronotype, a potential modifier between shift-induced circadian disruption and cardiometabolic outcomes. The main objective is to determine the association between night work parameters and cardiometabolic risk factors. The secondary objective is to assess how the association between night work parameters and cardiometabolic risk factors differs by chronotype. A cross-sectional study was conducted with 325 full- and part-time female hospital employees (168 rotating night workers, 157 day workers). Night work status, cumulative night work duration, and night work intensity were determined through self-report, and cardiometabolic risk factors were assessed through clinical exams. Chronotype was determined using the Munich Chronotype Questionniare (MCTQ). Multiple linear regression was used to examine the association between night work parameters and cardiometabolic risk factors. Current night work, cumulative night work, and night work intensity are associated with a number of cardiometabolic indices, including higher waist circumference, body mass index, fasting glucose, blood pressure, and cardiometabolic risk score. When stratified by chronotype, night work parameters are associated with a number of cardiometabolic risk factors in the evening-oriented chronotype subgroup. There is no difference in cardiometabolic risk factors in morning-oriented chronotypes when comparing night work parameters, with the exception of LDL cholesterol. These results suggest that night work parameters are associated with cardiometabolic risk, and night workers with an evening-oriented chronotype may be more susceptible to the adverse cardiometabolic impacts of night work. Future studies should consider chronotype when examining the relationship between night work and cardiometabolic risk.     

The cost of circadian desynchrony: Evidence,insights and open questions

Coordinated daily rhythms are evident in most aspects of our physiology, driven by internal timing systems known as circadian clocks. Our understanding of how biological clocks are built and function has grown exponentially over the past 20 years. With this has come an appreciation that disruption of the clock contributes to the pathophysiology of numerous diseases, from metabolic disease to neurological disorders to cancer. However, it remains to be determined whether it is the disruption of our rhythmic physiology per se (loss of timing itself), or altered functioning of individual clock components that drive pathology. Here, we review the importance of circadian rhythms in terms of how we (and other organisms) relate to the external environment, but also in relation to how internal physiological processes are coordinated and synchronized. These issues are of increasing importance as many aspects of modern life put us in conflict with our internal clockwork.

     

Occupation and risk of prostate cancer in Canadian men: A case-control study across eight Canadian provinces

BackgroundThe etiology of prostate cancer continues to be poorly understood, including the role of occupation. Past Canadian studies have not been able to thoroughly examine prostate cancer by occupation with detailed information on individual level factors.MethodsOccupation, industry and prostate cancer were examined using data from the National Enhanced Cancer Surveillance System, a large population-based case-control study conducted across eight Canadian provinces from 1994 to 1997. This analysis included 1737 incident cases and 1803 controls aged 50 to 79 years. Lifetime occupational histories were used to group individuals by occupation and industry employment. Odds ratios and 95% confidence intervals were calculated and adjustments were made for known and possible risk factors.ResultsBy occupation, elevated risks were observed in farming and farm management (OR = 1.37, 95% CI 1.02–1.84), armed forces (OR = 1.33, 95% CI 1.06-1.65) and legal work (OR = 2.58, 95% CI 1.05–6.35). Elevated risks were also observed in office work (OR = 1.20, 95% CI 1.00–1.43) and plumbing (OR = 1.77, 95% CI 1.07–2.93) and with ≥10 years duration of employment. Decreased risks were observed in senior management (OR = 0.65, 95% CI 0.46–0.91), construction management (OR = 0.69, 95% CI 0.50–0.94) and travel work (OR = 0.37, 95% CI 0.16–0.88). Industry results were similar to occupation results, except for an elevated risk in forestry/logging (OR = 1.54, 95% CI 1.06–2.25) and a decreased risk in primary metal products (OR = 0.70, 95% CI 0.51–0.96).ConclusionThis study presents associations between occupation, industry and prostate cancer, while accounting for individual level factors. Further research is needed on potential job-specific exposures and screening behaviours.     

Occupational exposure to petroleum-based and oxygenated solvents and oral and oropharyngeal cancer risk in men: A population-based case-control study in France

ObjectiveTo examine the association between occupational exposure to petroleum-based and oxygenated solvents and the risk of oral and oropharyngeal cancer.MethodsThe ICARE study is a large population-based case-control study conducted in France between 2001 and 2007. This present analysis was restricted to men and included 350 and 543 cases of squamous cell-carcinoma of the oral cavity and oropharynx, respectively, and 2780 controls. Lifetime tobacco, alcohol consumption and complete occupational history were assessed through detailed questionnaires. Job-exposure matrices allowed us to assess occupational exposure to five petroleum-based solvents (white spirits; diesel/fuel oils/kerosene; gasoline; benzene; special petroleum products) and five oxygenated solvents (diethyl ether; tetrahydrofuran; ketones and esters; alcohols; ethylene glycol). Odds-ratios (ORs), adjusted for age, smoking, alcohol consumption and socioeconomic status, and 95% confidence intervals (CI) were estimated using unconditional logistic models.ResultsAssociations between oral cancer risk and exposure to white spirits and diesel/fuel oils/kerosene were suggested, but there was no exposure-response trend. Concerning exposure to oxygenated solvents, participants with the highest levels of cumulative exposure to diethyl ether had a significant excess risk of oropharyngeal cancer (OR = 7.78, 95%CI 1.42 to 42.59; p for trend = 0.04). Ever exposure to tetrahydrofuran was associated with a borderline significant increased risk of oral cancer (OR = 1.87, 95%CI 0.97 to 3.61), but no exposure-response trend was observed. Additional adjustments for exposure to other solvents did not substantially change the results.ConclusionOur results do not provide evidence for a major role of petroleum-based and oxygenated solvents in the occurrence of oral and oropharyngeal cancers in men.