Sleep and cancer: Synthesis of experimental data and meta-analyses of cancer incidence among some 1,500,000 study individuals in 13 countries.

Sleep and its impact on physiology and pathophysiology are researched at an accelerating pace and from many different angles. Experiments provide evidence for chronobiologically plausible links between chronodisruption and sleep and circadian rhythm disruption (SCRD), on the one hand, and the development of cancer, on the other. Epidemiological evidence from cancer incidence among some 1 500 000 study individuals in 13 countries regarding associations with sleep duration, napping or "poor sleep" is variable and inconclusive. Combined adjusted relative risks (meta-RRs) for female breast cancer, based on heterogeneous data, were 1.01 (95% CI: 0.97-1.06). Meta-RRs for cancers of the colorectum and of the lung in women and men and for prostate cancer were 1.08 (95% CI: 1.03-1.13), 1.11 (95% CI: 1.00-1.22) and 1.05 (95% CI: 0.83-1.33), respectively. The significantly increased meta-RRs for colorectal cancer, based on homogeneous data, warrant targeted study. However, the paramount epidemiological problem inhibiting valid conclusions about the associations between sleep and cancer is the probable misclassification of the exposures to facets of sleep over time. Regarding the inevitable conclusion that more research is needed to answer How are sleep and cancer linked in humans? we offer eight sets of recommendations for future studies which must take note of the complexity of multidirectional relationships.

[Reduction of 137caesium contamination in wild boars by supplementing offered food with ammonium-iron-hexa-cyanoferrate]. / Reduktion der 137Cäsium-Aktivität in Wildschweinen durch Zusatz von Ammonium-Eisen-Hexacyanoferrat ("Berliner Blau") zum Kirrfutter.

OBJECTIVE: This replication study investigated whether the 137caesium (137Cs) contamination of wild boars could be relevantly reduced under field conditions by adding ammonium-iron-hexa-cyanoferrate (AFCF; Prussian blue) to the food. MATERIAL AND METHODS: In 285 wild boars that had been shot in six Bavarian hunting territories during the season (November until May) between 01 November 2010 and 10 December 2011 137Cs contamination was analysed. Thirty-five animals originated from two hunting territories in which offered food had been supplemented with 1250 mg AFCF per kilogram food. RESULTS: The control animals showed a mean 137Cs contamination of 522 Bq/kg lean skeletal muscle meat. Direct (univariable) comparisons of the two experimental territories with the four control territories yielded a mean reduction in 137Cs contamination due to Prussian bluefeeding by -211 Bq/kg (p < 0.001). Multivariable models that took potential confounders into account (age, weight, sex, hunting date, territory) estimated the effect to be -344 Bq/kg (p < 0.05). CONCLUSION AND CLINICAL RELEVANCE: This replication study confirmed the finding of Kienzle et al. (12) who described a statistically significant reduction in 137Cs contamination by -380 Bq/kg due to the feeding of Prussian blue in other territories.

Effect of ammonium-iron-hexa-cyanoferrate and of the covariates age, gender, weight, season and calendar time on radiocaesium contamination of wild boars living in the wild in Bavaria.

Feed with Ammonium-iron-hexa-cyanoferrate (AFCF; 1250 mg AFCF/kg) was fed between March 2009 and March 2011 to wild boars in a territory of 4.5 km(2) (experimental group, EXP). One hundred and forty similar territories in the same county (500 km(2) , spruce forest, agriculture) served as control (CON). Data for comparison from all territories were available from March 2005 to March 2011. Wild boars could move between, into and from the territories. Lean skeletal muscle meat (500 g) of all wild boars that were killed by humans (hunting and traffic accidents) was investigated for gamma-radiation from (137) Cs with a becquerel monitor with a sodium iodide scintillator crystal (range of detection 20-9999 Bq/kg). The wild boars were weighed, and gender and age were determined. For the analyses of effects, multivariable regression models were fitted with the (137) Cs concentration as response variable. There was a significant difference between the (137) Cs contamination of wild boars from CON (563 ± 932 Bq/kg meat, n = 1253) and EXP (236 ± 276 Bq/kg meat; n = 45). (137) Cs contamination decreased with increasing body weight by -5 Bq/kg meat/kg body weight increase (p < 0.05). Females had higher Bq measurements than males (by +80 Bq/kg meat, p < 0.05). Piglets were lower than adults, but turn-coats higher. From November to May, contamination was higher (by +500 to +600 Bq/kg meat, p < 0.05) than during the rest of the year. In 2010, contamination was higher (by +200 to + 300 Bq/kg meat, p < 0.05) in comparison with the other years under observation. When all covariates were controlled for, the effect of AFCF was highly significant. Interaction analyses showed that the intervention decreased (137) Cs contamination by -500 Bq/kg meat during November to May and by -200 Bq/kg meat during the rest of the year. In summary, AFCF feeding reduces (137) Cs contamination of wild boars living in the wild significantly, particularly during the season from November to May.

Meta-analyses of published epidemiological studies, 1979-2006, point to open causal questions in silica-silicosis-lung cancer research.

BACKGROUND AND OBJECTIVES: Following up on a previous meta-analysis of lung cancer risk in individuals without silicosis, we provide more detailed results of silica associated lung cancer risk in both silicotics and non-silicotics. The objective was to examine in depth whether current data allows to answer the pressing question "does silica cause lung cancer in the absence of silicosis"? METHODS: We updated earlier meta-analyses of silicosis and lung cancer and compared the results with our 2009 meta-analysis of risks in individuals without silicosis. We performed fixed (FE) and random (RE) effects meta-analyses, calculated heterogeneity statistics, stratified the study material, performed sensitivity analyses with modified study results and meta-regressions to detect effect modification. RESULTS: In silicotics, lung cancer risks were found to be doubled in 38 studies (FE: RR = 2.1; 95% CI = 2.0-2.3). In non-silicotics, eight studies without smoking adjustment suggested marginally elevated risks (FE: RR = 1.2; 95% CI = 1.1-1.3; RE: RR = 1.2; 95% CI =1.0-1.4) but three studies which were controlled for smoking showed null results (FE and RE: RR = 1.0; 95% CI = 0.8-1.3). Heterogeneity was substantial but could be linked to study characteristics, like sector of industry, and other second-level data in meta-regression. As no excess was observe dfor other smoking-related effects in studies ofllung cancer among non-silicotics, smoking was not considered to be an important confounder or modifier. CONCLUSIONn: Our meta-analyses further substantiate evidence of a strong association between silicosis and lung cancer. However, questions remain regarding lung cancer caused by silica in non-silicotics. Ideally, future investigations should consider the entire exposure-response range between silica exposure, silicosis development and lung cancer occurrence, and analyze data in terms of processes taking intermediate confounding into account.

Effect of dust exposure and nitrogen oxides on lung function parameters of German coalminers: a longitudinal study applying GEE regression 1974-1998.

PURPOSE: Workplace limits for dust and nitrogen oxides are under review in Germany and the EU. We conducted a study on German coal miners to determine the effects of exposure on lung function. METHODS: Longitudinal inception cohort study (1974-1998) on miners who began working underground at two coal mines between 1974 and 1979. We determined the number of shifts worked underground, the exposure to coal mine dust, quartz dust, nitrogen oxides (NO, NO(2)), smoking behavior, and three lung function parameters (FVC, FEV(1), FEV(1)/FVC). General estimation equation (GEE) models were fitted. RESULTS: 1,369 miners worked an average 3,017 shifts (S) underground. The mean respirable coal mine dust concentration was 1.89 mg/m(3) (quartz: 0.067 mg/m(3)), and the nitrogen oxide concentrations were 0.58 ppm (NO) and 0.007 ppm (NO(2)). On average, 9 measurements of lung function were available per miner. Compared to reference values, the findings were unexceptionable (103, 101, and 99%) on average. GEE-regression models did not reveal detrimental dust exposure effects. Nitrogen oxides (NO (x) = NO + NO(2)) showed small but clearly insignificant effects on lung function: delta FVC = -0.0008 ml/(220 ppmS), P = 0.86, delta FEV(1) = -0.003 ml/(220 ppmS), P = 0.50 and delta FEV(1)%FVC = -0.07%/(220 ppmS), P = 0.22. CONCLUSIONS: The effect of dust exposure on lung function described in older British and American coal miner studies was not confirmed. This can be explained partly by differences in methods (here: longitudinal studies, no prior exposure), but also by lower dust levels. NO (x) exposures showed no relevant influence on lung function-a result confirming findings from British coal mining.

[Health effects of particulate matter exposure: current scientific knowledge]. / Gesundheitliche Effekte der Feinstaubbelastung - aktueller wissenschaftlicher Kenntnisstand.

INTRODUCTION: Air quality is not only important for respiratory health but it also influences the homeostasis of the whole human organism. In the past years numerous violations of European Union particulate matter thresholds have been recorded. METHODS: The present study is a selective literature analysis encompassing the epidemiology and pathophysiological effects of particulate matter. RESULTS: Epidemiological studies point to an association between chronic particulate matter exposure and mortality. The most prominent effects on the human body are present in subjects with cardiovascular or respiratory conditions. However, the effects of air pollutants need to be examined critically and the plausibility of thresholds should be evaluated in detail. DISCUSSION: The negative influences of chronic particulate matter exposure have been proven by a multitude of epidemiological and experimental studies. From the viewpoint of primary prevention, air quality plays a crucial role. This encompasses both the outdoor compartment with particulate matter and other pollutants and the indoor compartment with tobacco smoke.

Years of Life Lost due to exposure: Causal concepts and empirical shortcomings.

Excess Years of Life Lost due to exposure is an important measure of health impact complementary to rate or risk statistics. I show that the total excess Years of Life Lost due to exposure can be estimated unbiasedly by calculating the corresponding excess Years of Potential Life Lost given conditions that describe study validity (like exchangeability of exposed and unexposed) and assuming that exposure is never preventive. I further demonstrate that the excess Years of Life Lost conditional on age at death cannot be estimated unbiasedly by a calculation of conditional excess Years of Potential Life Lost without adopting speculative causal models that cannot be tested empirically. Furthermore, I point out by example that the excess Years of Life Lost for a specific cause of death, like lung cancer, cannot be identified from epidemiologic data without assuming non-testable assumptions about the causal mechanism as to how exposure produces death. Hence, excess Years of Life Lost estimated from life tables or regression models, as presented by some authors for lung cancer or after stratification for age, are potentially biased. These points were already made by Robins and Greenland 1991 reasoning on an abstract level. In addition, I demonstrate by adequate life table examples designed to critically discuss the Years of Potential Life Lost analysis published by Park et al. 2002 that the potential biases involved may be fairly extreme. Although statistics conveying information about the advancement of disease onset are helpful in exposure impact analysis and especially worthwhile in exposure impact communication, I believe that attention should be drawn to the difficulties involved and that epidemiologists should always be aware of these conceptual limits of the Years of Potential Life Lost method when applying it as a regular tool in cohort analysis.

Cross sectional study on cytokine production (TNF-α, IL-8) in German coalminers with progressive massive fibrosis and in control miners using a rapid wholeblood assay.

Whole-blood release of tumour necrosis factor (TNF-α) and interleukin 8 (IL-8) was studied in 26 German ex-coalminers with progressive massive fibrosis (≥A, ILO 1980; cases) and 26 ex-miners free of pneumoconiosis (≤ 0/1; controls) using a simple wholeblood assay. Cases and controls were matched individually by age and duration of coalmine dust exposure (5-year window). Whole-blood cytokine release was determined (blinded to case control status) in incubations without additions (spontaneous) and with endotoxin (LPS, 3 ng ml(-1)) or with coalmine dust (CMD; 5 mg ml(-1)). CMD-stimulated TNF-α release was significantly increased and LPS-induced IL-8 release was significantly decreased in cases (matched t-tests: p < 0.01). No effect of duration of exposure was detectable in an unmatched analysis. No clear relationship with lung function parameters independent from case/control-status was observed, although a possible positive association with central airway resistance was indicated by multiple regression for both CMD stimulated TNF-α and LPS-stimulated IL-8. This study on individually matched coalminers validates previous findings on monocyte TNF release as a marker for pneumoconiosis using a method (whole-blood assay) that is more feasible for epidemiological studies. The different response of TNF-α and IL-8 may be useful in studying the occurrence of different endpoints like pneumoconiosis and lung function decrease.