Air pollution and molecular changes in age-related diseases.

Assessment of the impact that air contaminants have on health is difficult as this is a complex mixture of substances that varies depending on the time and place. There are many studies on the association between air pollution and increased morbidity and mortality. Before the effect of polluted air is manifested at the level of the organs, an impact can be observed at the molecular level. These include some new biomarkers, like a shortening of the mean telomere length in DNA, dysregulation of gene expression caused by microRNA levels or a variation in the copy number of mitochondrial DNA. These changes may predispose individuals to premature development of age-related diseases and consequently to shortening of life. The common attribute, shared by changes at the molecular level and the development of diseases, is the presence of oxidative stress.

Biological agents of bioterrorism - preparedness is vital.

Bioterrorist threats and attacks are still an issue of concern in the world. Biological agents are divided into three categories. The highest priority agents classified in category A pose a massive risk to public health and national security. The society should be prepared for this risk. Health professionals in the Czech Republic should be aware of the diseases caused by category A agents, which are not common in the country. In this context, the project of the Ministry of the Interior of the Czech Republic “Decontamination of the injured persons” has been implemented at the Faculty of Health Sciences, Palacký University, Olomouc. The article provides an overview of selected serious infectious risks and information on the project the aim of which is to create certified methodical procedures and guidelines on situations related to bioterrorism.

[Cat scratch disease - a neglected zoonosis]. / Nemoc z kocicího skrábnutí - opomíjená zoonóza.

Cat scratch disease is a relatively rare infection that is caused by the bacterium Bartonella henselae. This disease occurs after cat scratch or bite. The course of the disease depends on the patients immunity status. In immunocompetent patients, the disease typically runs as a lymph node syndrome. Sometimes, mild general symptoms may appear, or the course can be atypical with a more serious clinical manifestation involving various organs. In immunocompromised patients, Bartonella henselae can cause bacillary angiomatosis or peliosis with a severe course.

[Are risk factors in prenatal and perinatal period important for develompent of schizophrenia?] / Jsou rizikové faktory v prenatálním a perinatálním období dulezité pro vznik schizofrenie?

OBJECTIVE: Schizophrenia is an important psychical disease of multifactorial origin and not yet clear etiology. In prenatal and perinatal period some potential risk factors for schizophrenia are taken into consideration. DESIGN: Case-control study of 815 subjects, 407 cases and 408 controls was performed in 2013 to 2015. METHODS: In this study environmental and genetic risk factors were evaluated including potential risk factors of prenatal and perinatal period. RESULTS: Statistically important difference was found in child-birth done by cesarean section (p = 0.009) and in patients with schizophrenia were 15.7% complications in the course of childbirth (p < 0.001). Hypoxia, passed umbilical cord were the most frequent complications. In prenatal period premature childbirth, injury and psychical complications were the most frequent. On the other hand difference in weight and length of newborns, breast feeding and infection during pregnancy were found not statistically important. CONCLUSION: In this study statistically important diference were found in way of carrying childbirth and in some complications during pregnancy and delivery. Influence of infection during pregnancy and influence of weight and length of newborn were not demonstrated.

High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients.

Background: Exosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). Patients and methods: Patient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13. A cumulative series of 263 individuals were studied, including a discovery cohort of 142 individuals: 68 PDAC patients of all stages; 20 PDAC patients initially staged with localized disease, with blood drawn after resection for curative intent; and 54 age-matched healthy controls. A validation cohort of 121 individuals (39 cancer patients and 82 healthy controls) was studied to validate KRAS detection rates in early-stage PDAC patients. Primary outcome was circulating KRAS status as detected by droplet digital PCR. Secondary outcomes were disease-free and overall survival. Results: KRAS mutations in exoDNA, were identified in 7.4%, 66.7%, 80%, and 85% of age-matched controls, localized, locally advanced, and metastatic PDAC patients, respectively. Comparatively, mutant KRAS cfDNA was detected in 14.8%, 45.5%, 30.8%, and 57.9% of these individuals. Higher exoKRAS MAFs were associated with decreased disease-free survival in patients with localized disease. In the validation cohort, mutant KRAS exoDNA was detected in 43.6% of early-stage PDAC patients and 20% of healthy controls. Conclusions: Exosomes are a distinct source of tumor DNA that may be complementary to other liquid biopsy DNA sources. A higher percentage of patients with localized PDAC exhibited detectable KRAS mutations in exoDNA than previously reported for cfDNA. A substantial minority of healthy samples demonstrated mutant KRAS in circulation, dictating careful consideration and application of liquid biopsy findings, which may limit its utility as a broad cancer-screening method.

[A report of 10 cases of familial Creutzfeld-Jakob disease]. / Popis familiární formy Creutzfeldt-Jakobovy nemoci.

AIM: The analysis of the available reported data and epidemiological investigation data on the cases of Creutzfeld-Jakob disease (CJD) that emerged in the Nový Jicín district in 2001-2011, with a focus on the familial form of the disease. MATERIAL AND METHODS: Data from the Regional Public Health Service of the Moravian-Silesian Region, local Public Health Centre Nový Jicín, were used for the analysis. RESULTS: This is a retrospective report of 10 cases of familial Creutzfeld-Jakob disease (CJD) in the Nový Jicín district in 2001-2011, based on the data from the public health service. Overall eight cases were notified and seven suspected cases were identified retrospectively. Out of these 15 cases, five were concluded to be sporadic CJD and 10 to be familial CJD. The PRNP D178N mutation was found in two fatal cases from 2002 and 2003. Genetic investigation of their relatives was not performed for ethical reasons. CONCLUSION: The high incidence of familial CJD in the Nový Jicín district in 2001-2011 is surprising, but the retrospective investigation failed to provide further evidence to understand this outbreak.

Evaluation of Dietary Habits in the Study of Pancreatic Cancer.

BACKGROUND: Pancreatic cancer is serious and rapidly progressing condition. Little is known about the role of diet in etiology of pancreatic cancer. The study focused on the role of selected dietary factors related to pancreatic cancer. MATERIAL AND METHODS: The case-control study was performed in the Czech Republic in 2006- 2009, involving three centers in Olomouc, Ostrava and Ceske Budejovice. It comprised a total of 530 persons, of whom 310 had pancreatic cancer and 220 were controls. Data were obtained directly from each participant in an interview with a trained interviewer and entered into a standardized questionnaire. The data were analyzed using a crude odds ratio (OR) and multivariate logistic regression with an adjusted OR and 95% CI. The statistical analysis was performed with the STATA v. 10 software. RESULTS: A very strong protective effect was found in pickled cabbage (OR 0.32; 95% CI 0.19- 0.55), broccoli (OR 0.37; 95% CI 0.25- 0.53), cooked onion (OR 0.14; 95% CI 0.08- 0.27), tomatoes (OR 0.28; 95% CI 0.13- 0.60), raw carrot (OR 0.33; 95% CI 0.20- 0.56), cooked carrot (OR 0.35; 95% CI 0.19- 0.62). In logistic regression model, statistically significant protective associations were found in consumption of more than three portions of cooked vegetables per week (OR 0.16; 95% CI 0.05- 0.55) and high consumption of citrus fruit (OR 0.46; 95% CI 0.23- 0.90). CONCLUSION: The study found statistically significant protective effect of consumption of more than three portions of cooked vegetables per week and high consumption of citrus fruit.

[A multifactor epidemiological analysis of risk factors for pancreatic cancer in women]. / Multifaktorová epidemiologická analýza rizikových faktoru karcinomu pankreatu u zen.

STUDY OBJECTIVE: A multifactor analysis of risk factors for pancreas cancer in women. MATERIAL AND METHODS: A case-control study was conducted in three centres in the Czech Republic (Olomouc, Ostrava, and Ceské Budejovice) in 2006-2009. In total, 226 women (129 pancreas cancer cases, 97 controls) were included in the study. Statistical analysis was performed, the crude odds ratio (OR) was calculated, and logistic regression analysis was used at a 5% level of statistical significance. RESULTS: A statistically significant inverse association was found between pancreatic cancer and oral contraceptives (OR 0.21; 95% CI: 0.07-0.69). Pregnancy and number of pregnancies or gynecological surgical procedures did not show any association with pancreatic cancer. No significant difference in the first menstrual period was found between pancreatic cancer patients and controls. CONCLUSIONS: The study results showed inverse association between pancreatic cancer and oral contraceptives (OR 0.21; 95% CI: 0.07-0.69), controlled alcohol consumption (OR 0.26; 95% CI: 0.12-0.55), and anti-inflamatory drug use (OR 0.10; 95% CI: 0.02-0.41).

[Epidemiology and risk factors in legionellosis]. / Epidemiologie a rizikové faktory u legionelózy.

Legionella was discovered in the first half of the 20th century. The main representative of the genus is the bacterial species Legionella pneumophila. Legionella can cause a mild disease with fever but also severe to fatal pneumonia. At highest risk are individuals with an underlying disease, immunosuppressed patients or individuals exposed to other risk factors (e.g. users of addictive substances). Information on the etiology and epidemiology of legionellosis is presented. Selected risk factors are described as well as preventive measures to be taken in water supply and cooling systems. In conclusion, emphasis is placed on the prevention.

Is physical activity a protective factor against pancreatic cancer?

OBJECTIVES: The objective of the study was to analyze an association between selected factors and pancreatic cancer, assuming that knowing the etiology would help influence the incidence of this severe type of cancer through primary prevention. In addition to age, gender, BMI and education, the analysis aimed at assessing occupational and leisure-time physical activities with respect to pancreatic cancer. BACKGROUND: In numerous studies, physical activity is reported to be a protective factor against pancreatic cancer. METHODS: A case-control study was carried out in three centers in the Czech Republic in 2006-2009. RESULTS: The study comprised a total of 529 individuals, of which 309 were patients with pancreatic cancer and 220 were controls. Leisure-time physical activity showed a statistically significant inverse association with a crude odds ratio of 0.65 (95% CI 0.45-0.93), even after adjustment for other studied factors (OR =0.63, 95% CI 0.43-0.92). Conversely, for occupational physical activity, a positive association was only suggested. CONCLUSIONS: Leisure-time physical activity is a protective factor against the development of pancreatic cancer. Occupational physical activity was not confirmed as a protective factor against pancreatic cancer (Tab. 4, Fig. 1, Ref. 22).

[A new strategy in the surgical treatment of multiple liver tumors - ALPPS]. / Nová strategie chirurgické lécby mnohocetného nádorového postizení jater - ALPPS.

INTRODUCTION: This systematic review was performed to introduce the two-staged hepatectomy procedure (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy - ALPPS) and present its current results. MATERIAL AND METHODS: We conducted a systematic literature search using the PubMed database with key words "ALPPS" or "staged liver resection". The inclusion criteria were randomized trials or cohort studies. Case reports were excluded. The primary end-point was the assessment of liver tissue hypertrophy after the ALPPS procedure. Morbidity and mortality evaluation were the secondary end-point. RESULTS: After an electronic data search of PubMed with the selected key words, six cohort studies evaluating 96 patients met the inclusion criteria. There was no prospective randomised trial. Based on the results of the individual studies, liver hypertrophy ranged from 74 to 87%. Morbidity and mortality ranged from 53 to 71% and 0 to 13% respectively. CONCLUSIONS: Despite the higher morbidity and mortality the ALPPS procedure could be a promising technique for a selected group of patients with multiple liver tumors. However long term results are not yet available.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

[Pancreatic cancer and lifestyle factors]. / Karcinom pankreatu a faktory zivotního stylu.

BACKGROUND: Pancreatic cancer is a serious cancer with unfavorable prognosis. Due to differences in the incidence of pancreatic cancer in different regions, it is clear that factors associated with lifestyle play an important role in the etiology. The aim of this study was to evaluate the impact of selected lifestyle factors in relation to pancreatic cancer. MATERIALS AND METHODS: The study included a total of 529 subjects, including 309 cases and 220 control subjects. Cases of newly diagnosed patients with pancreatic cancer who lived in the region were selected in hospitals in three centers (University Hospital Olomouc, University Hospital Ostrava, Hospital Ceske Budejovice). The control group was obtained in cooperation with selected general practitioners for adults, and it is a population control group. RESULTS: Analyses compared persons who reported consuming alcohol with those who do not consume alcohol. Results showed a statistically significant inverse association, even after adjustment for the other studied factors (OR = 0.57, 95% CI 0.36 to 0.89). When assessing leisure time physical activity, results showed statistically significant inverse association and 35% decrease in the risk (crude OR = 0.65, 95% CI 0.45 to 0.93), and this inverse association was confirmed after adjustment for other studied factors although the result is on the border of statistical significance (adjusted OR = 0.68, 95% CI 0.44 to 1.04). Drinking coffee and tea has only a marginal impact on the occurrence of pancreatic cancer, although the medium and high consumption of black tea was found increased risk by 90 or 44%, respectively. Smoking is considered a causal risk factor for pancreatic cancer, but in this study, a positive association was not found. The study found no statistically significant association between overweight and obesity. CONCLUSION: Physical activity, dietary measures that will lead to weight loss and education to non-smoking can have a significant impact on the primary prevention of cancer.

Indoor air pollution from solid fuels and risk of upper aerodigestive tract cancers in central and eastern Europe.

BACKGROUND: Indoor air pollution from solid fuels is a potentially important risk factor for cancer, yet data on cancers from organs other than the lung are scarce. We investigated if indoor air pollution from coal and wood are risk factors for additional cancers, particularly that of the upper aerodigestive tract (oral cavity, larynx, pharynx and esophagus) in the high-risk areas of central and eastern Europe. METHODS: We used data from multi-center hospital-based case-control study of 1065 histologically confirmed upper aerodigestive tract cancer cases and 1346 controls. Standardized questionnaires were used to collect information on residential fuel use for cooking and heating. Using unconditional logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for upper aerodigestive tract cancer risk after adjusting for potential confounders. RESULTS: Lifelong wood use was associated with pharyngeal and esophageal (OR 4.05, 95% CI: 1.30-12.68 and OR 2.71, 95% CI: 1.21-6.10, respectively). We observed an exposure-response relationship between duration of wood use and risk of pharyngeal cancer among those who had never used coal (P(trend)=0.04), ruling out the possibility of residual confounding by coal. Similarly, we observed an increased risk of laryngeal cancers and head & neck cancers among those who always used coal, with a noted exposure-response relationship (P(trend)<0.01). CONCLUSIONS: Our results suggest a possible role of indoor air pollution from solid fuel use in head and neck carcinogenesis in the high risk area of central and eastern Europe.

Genomic copy number alterations in clear cell renal carcinoma: associations with case characteristics and mechanisms of VHL gene inactivation.

Array comparative genomic hybridization was used to identify copy number alterations in clear cell renal cell carcinoma (ccRCC) patient tumors to identify associations with patient/clinical characteristics. Of 763 ccRCC patients, 412 (54%) provided frozen biopsies. Clones were analyzed for significant copy number differences, adjusting for multiple comparisons and covariates in multivariate analyses. Frequent alterations included losses on: 3p (92.2%), 14q (46.8%), 8p (38.1%), 4q (35.4%), 9p (32.3%), 9q (31.8%), 6q (30.8%), 3q (29.4%), 10q (25.7%), 13q (24.5%), 1p (23.5%) and gains on 5q (60.2%), 7q (39.6%), 7p (30.6%), 5p (26.5%), 20q (25.5%), 12q (24.8%), 12p (22.8%). Stage and grade were associated with 1p, 9p, 9q, 13q and 14q loss and 12q gain. Males had more alterations compared with females, independent of stage and grade. Significant differences in the number/types of alterations were observed by family cancer history, age at diagnosis and smoking status. Von Hippel-Lindau (VHL) gene inactivation was associated with 3p loss (P

Occupational exposure to dusts and risk of renal cell carcinoma.

BACKGROUND: Occupational exposures to dusts have generally been examined in relation to cancers of the respiratory system and have rarely been examined in relation to other cancers, such as renal cell carcinoma (RCC). Although previous epidemiological studies, though few, have shown certain dusts, such as asbestos, to increase renal cancer risk, the potential for other occupational dust exposures to cause kidney damage and/or cancer may exist. We investigated whether asbestos, as well as 20 other occupational dust exposures, were associated with RCC risk in a large European, multi-center, hospital-based renal case-control study. METHODS: General occupational histories and job-specific questionnaires were reviewed by occupational hygienists for subject-specific information. Odds ratios (ORs) and 95% confidence intervals (95% CIs) between RCC risk and exposures were calculated using unconditional logistic regression. RESULTS: Among participants ever exposed to dusts, significant associations were observed for glass fibres (OR: 2.1; 95% CI: 1.1-3.9), mineral wool fibres (OR: 2.5; 95% CI: 1.2-5.1), and brick dust (OR: 1.5; 95% CI: 1.0-2.4). Significant trends were also observed with exposure duration and cumulative exposure. No association between RCC risk and asbestos exposure was observed. CONCLUSION: Results suggest that increased RCC risk may be associated with occupational exposure to specific types of dusts. Additional studies are needed to replicate and extend findings.

TP53, EGFR, and KRAS mutations in relation to VHL inactivation and lifestyle risk factors in renal-cell carcinoma from central and eastern Europe.

Renal-cell carcinomas (RCC) are frequent in central and eastern Europe and the reasons remain unclear. Molecular mechanisms, except for VHL, have not been much investigated. We analysed 361 RCCs (334 clear-cell carcinomas) from a multi-centre case-control study for mutations in TP53 (exons 5-9 in the whole series and exons 4 and 10 in a pilot subset of 60 tumours) and a pilot 50 tumours for mutations in EGFR (exons 18-21) or KRAS (codon 12) in relation to VHL status. TP53 mutations were detected in 4% of clear-cell cases, independently of VHL mutations. In non-clear-cell carcinomas, they were detected in 11% of VHL-wild-type tumours and in 0% of tumours with VHL functional mutations. No mutations were found in EGFR or KRAS. We conclude that mutations in TP53, KRAS, or EGFR are not major contributors to the RCC development even in the absence of VHL inactivation. The prevalence of TP53 mutations in relation to VHL status may differ between clear-cell and other renal carcinomas.

Vitamin d pathway genes, diet, and risk of renal cell carcinoma.

Mediated by binding to the high-affinity vitamin D receptor (VDR), vitamin D forms a heterodimer complex with the retinoid-X-receptor (RXR). Variation in both genes has been shown to modify renal cell carcinoma (RCC) risk. Therefore, we investigated whether VDR and RXRA polymorphisms modify associations between RCC risk and frequency of dietary intake of vitamin D and calcium rich foods, and occupational ultraviolet exposure among 777 RCC case and 1035 controls from Central and Eastern Europe. A positive association was observed in this population between increasing dietary intake frequency of yogurt, while an inverse association was observed with egg intake frequency. RXRA polymorphisms, located 3' of the coding sequence, modified associations between specific vitamin D rich foods and RCC risk, while RXRA polymorphisms, located in introns 1 and 4, modified associations with specific calcium rich foods. Results suggest that variants in the RXRA gene modified the associations observed between RCC risk and calcium and vitamin D intake.

Occupation and renal cell cancer in Central and Eastern Europe.

OBJECTIVE: Central and Eastern Europe has among the highest rates of renal cell cancer worldwide. Few studies have been conducted in these areas to investigate the possible role of occupational exposures in renal cell cancer aetiology. The purpose of this study was to examine the association of renal cell cancer with employment in specific occupations and industries. METHODS: From 1999 to 2003, we conducted a hospital-based case-control study in seven areas of the Czech Republic, Poland, Romania and Russia. A detailed occupational history was collected from renal cell cancer cases and controls, together with information on potential confounders. Odds ratios (ORs) and 95% CI of cancer risk were calculated for having ever been employed in selected jobs and industries, with follow-up analyses examining duration of employment. RESULTS: A total of 992 histologically confirmed incident renal cell cancer cases and 1459 controls were included in the analysis. An increased risk of renal cell cancer was observed for workers in agricultural labour and animal husbandry (OR 1.43; 95% CI 1.05 to 1.93), particularly among women employed as general farm workers (OR 2.73; 95% CI 1.05 to 7.13). Risk gradients for agricultural work increased with longer employment. An overall increased risk of renal cell cancer was seen among architects and engineers (OR 1.89; 95% CI 1.35 to 2.65), and mechanical engineers (OR 1.71; 95% CI 1.03 to 2.84). CONCLUSIONS: Our data suggest an association between renal cell cancer and agricultural work, particularly among female workers.

Tobacco smoking, body mass index, hypertension, and kidney cancer risk in central and eastern Europe.

In a case-control study of kidney cancer in four central European countries, with 1097 incident cases and 1476 controls, we found an increased risk for self-reported hypertension and for obesity. Additional unknown risk factors are likely to be responsible for the high rates of kidney cancer in this region.