Polymorphisms of DNA repair genes and lung cancer in chromium exposure.

Chromium is a well known carcinogen involved in the lung cancer development. Polymorphism of some of the DNA repair genes may be associated with elevated risk of cancerous transformation. In the present study, we investigated the polymorphisms of the following selected members of the base and nucleotide excision repair genes: XPC (Lys939Gln), XPD (Lys751Gln), XRCC1(Arg399Gln), and hOGG1(Ser326Ser), and the risk they present toward the development of lung cancer, with emphasis on the effect of chromium exposure. We analyzed 119 individuals; 50 patients exposed to chromium with diagnosed lung cancer and 69 healthy controls. Genotypes were determined by a PCR-RFLP method. We found a significantly increased risk of lung cancer development in XPD genotype Lys/Gln (OR=1.94; 95% CI=1.10-3.43; p=0.015) and in the gene combinations: XPD Lys/Gln+XPC Lys/Gln (OR=6.5; 95% CI=1.53-27.49; p=0.009) and XPD Lys/Gln+XPC Gln/Gln(OR=5.2; 95% CI=1.07-25.32; p=0.04). In conclusion, gene polymorphisms in the DNA repair genes may underscore the risk of lung cancer development in the chromium-exposed individuals.

Mismatch repair gene polymorphisms and association with lung cancer development.

hMLH1 and hMSH2 are two of the main members of the mismatch repair (MMR) genes family. Polymorphism of MMR genes is associated with a risk of developing sporadic and hereditary tumors. In the present case-control study, we investigated the promoter polymorphisms of selected mismatch repair genes: hMLH1 (rs1800734) and hMSH2 (rs2303425), and the risk they present regarding the development of lung cancer in the Slovak population. The study included 422 lung cancer cases, 511 controls for hMLH1 gene and 486 controls for hMSH2 gene. Polymorphism was investigated by a PCR-RFLP method. The risk of cancer development was evaluated in both dominant and recessive genetic models. The evaluation of rs1800734 polymorphism in patients in the dominant model showed a significantly decreased risk of lung cancer in the presence of at least one variant allele A (genotype GA and AA) (OR=1.40; 95% CI=1.08-1.82; p=0.01). These findings were equally strong expressed in women (OR=2.00; 95% CI=1.23-3.25; p=0.006). The results for rs2303425 polymorphism revealed an increased risk of lung cancer for variant genotype CC (OR=2.28; 95% CI=1.12-4.63; p=0.024) in the recessive model. A combination of rs1800734 and rs2303425 polymorphisms was shown to be risky for genotype GGCC; OR=3.08; 95% CI=1.09-8.72; p=0.03. The risk appeared even greater in female gender; (OR=11.56; 95% CI=1.33-100.36, 1.26-94.66; p=0.005. We conclude that the genotype of mismatch repair genes underscores the risk of lung cancer development in the Slovak population.

DNA repair genes polymorphism and lung cancer risk with the emphasis to sex differences.

Polymorphisms in nucleotide and base excision repair genes are associated with the variability in the risk of developing lung cancer. In the present study, we investigated the polymorphisms of following selected DNA repair genes: XPC (Lys939Gln), XPD (Lys751Gln), hOGG1 (Ser326Cys) and XRCC1 (Arg399Gln), and the risks they present towards the development of lung cancer with the emphasis to gender differences within the Slovak population. We analyzed 761 individuals comprising 382 patients with diagnosed lung cancer and 379 healthy controls. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism method. We found out statistically significant increased risk for lung cancer development between genders. Female carrying XPC Gln/Gln, XPC Lys/Gln+Gln/Gln and XRCC1 Arg/Gln, XRCC1 Arg/Gln+Gln/Gln genotypes had significantly increased risk of lung cancer corresponding to OR = 2.06; p = 0.04, OR = 1.66; p = 0.04 and OR = 1.62; p = 0.04, OR = 1.69; p = 0.02 respectively. In total, significantly increased risk of developing lung cancer was found in the following combinations of genotypes: XPD Lys/Gln+XPC Lys/Lys (OR = 1.62; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 2.14; p = 0.02). After stratification for genders, the following combinations of genotype were found to be significant in male: XPD Lys/Gln+XPC Lys/Lys (OR = 1.87; p = 0.03), XRCC1 Arg/Gln+XPC Lys/Lys (OR = 4.52; p = 0.0007), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 5.44; p < 0.0001). In female, different combinations of the following genotypes were found to be significant: XRCC1 Arg/Gln+hOGG1 Ser/Ser (OR = 1.98; p = 0.04), XRCC1 Gln/Gln+hOGG1 Ser/Ser (OR = 3.75; p = 0.02), XRCC1 Arg/Gln+XPC Lys/Gln (OR = 2.40; p = 0.04), XRCC1 Arg/Gln+XPC Gln/Gln (OR = 3.03; p = 0.04). We found out decreased cancer risk in genotype combinations between female patients and healthy controls: XPD Lys/Lys+XPC Lys/Gln (OR = 0.45; p = 0.02), XPD Lys/Gln+XPC Lys/Lys (OR = 0.32; p = 0.005), XPD Lys/Gln+XPC Lys/Gln (OR = 0.48; p = 0.02). Our results did not show any difference between pooled smokers and non-smokers in observed gene polymorphisms in the association to the lung cancer risk. However, gender stratification indicated the possible effect of heterozygous constitution of hOGG1 gene (Ser/Cys) on lung cancer risk in female non-smokers (OR = 0.20; p = 0.01) and heterozygous constitution of XPC gene (Lys/Gln) in male smokers (OR = 2.70; p = 0.01).

Trends in the lung cancer incidence and mortality in the Slovak and Czech Republics in the contexts of an international comparison

INTRODUCTION: Lung cancer represents the most frequent cause of cancer-related deaths in the industrialized countries. The aim of this study was to analyze the lung cancer incidence and mortality and the possible reasons for any differences discovered in two neighboring Central European countries-the Slovak Republic. METHODS: We used linear regression model when analyzing incidence and mortality; the trends are presented with corresponding 95% confidence intervals (CI) and p-value with null hypothesis being constant with time. RESULTS: Statistically significant increase of age-standardized incidence (0.707/100,000/year, 95% CI 0.107-1.307, p = 0,025) and mortality (1.339/100,000/year, 95% CI 1.050-1.629, p < 0.0001) of the lung cancer was revealed in males in the Slovak Republic (1980-1991). On the contrary, values of both indicators were stabilized in the Czech Republic. Since year 1991-2005 a statistically highly significant decrease of both incidence and mortality values was observed in males, which was greater in the Slovak Republic. Peak of the curve was not reached in women population, while incidence and mortality values have significantly continuous growth in both countries. CONCLUSIONS: According to the lung cancer incidence and mortality trends in both countries (in correlation with smoking prevalence) we consider the support of efforts to change the attitude towards smoking predominantly in women and younger generation to be the most accurate action to reduce these trends (AU)

Lung adenocarcinoma and squamous cell carcinoma in association with genetic polymorphisms of GSTs in Slovak population.

Slovak Republic belongs to the countries with high incidence of lung cancer. Gene polymorphisms of the glutathione S-transferases (GSTs) may play a role in individual lung cancer susceptibility. In presented case-control study we investigate the incidence of polymorphism of GSTT1, GSTM1, GSTP1 genes and their combinations as possible predictive factors for identification of individuals with increased risk of formation and development of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of lung in Slovak population. The study was conducted on 520 individuals consisting of 118 patients with adenocarcinoma, 112 patients with squamous cell carcinoma and 290 control individuals. GSTT1, GSTM1, GSTP1 gene polymorphisms were assayed by standard PCR and PCR-RFLP technique. The results of this study indicate that the GSTT1null-genotype and combination GSTT1 null and Ile/Val or Val/Val are associated with increased risk of lung adenocarcinoma. A significant association with 2.13 - fold increased risk was observed between lung adenocarcinoma and GSTT1 null genotype (95% CI = 1.29 - 3.51; p= 0.004). Also it was proved 2.83 times statistically higher risk for development of this histological type of lung cancer (95% CI = 1.34 - 6.01; P= 0.005) in combination of GSTT1null and Ile/Val or Val/Val genotypes. GSTT1, GSTM1, GSTP1 polymorphism did not show any significant association with SCC. Our study suggests that genetic make-up in metabolizing genes may increase susceptibility towards lung cancer development.

Lung cancer incidence and survival in chromium exposed individuals with respect to expression of anti-apoptotic protein survivin and tumor suppressor P53 protein.

OBJECTIVE: Workers chronically exposed to hexavalent chromium have elevated risk of lung cancer. Our study investigates the incidence of lung cancer types, age at onset of the disease, and survival time among chromium exposed workers with respect to the expression of anti-apoptotic p53 and pro-apoptotic survivin proteins. MATERIAL AND METHODS: 67 chromium exposed workers and 104 male controls diagnosed with lung cancer were analyzed. The mean exposure time among workers was 16.7 ±10.0(SD) years (range 1- 41 years). To investigate the possible regulation of survivin by p53 we examined the expression of both proteins using immohistochemical visualization. RESULTS: Chromium exposure significantly decreases the age of onset of the disease by 3.5 years (62.2 ±9.1 in the exposed group vs. 65.7 ±10.5 years in controls; P=0.018). Small cell lung carcinoma (SCLC) amounted for 25.4% of all cases in chromium exposed workers and for 16.3% in non-exposed individuals. The mean survival time in the exposed group was 9.0 ±12.7 vs. 12.1 ±21.9 months in controls, but this difference was not significant. Survivin was predominantly expressed in both cell nucleus and cytoplasm, whereas p53 was expressed in the nucleus. There was a negative correlation between survivin and p53 expression. A decreased intensity of expression and fewer cells positive for survivin was detected in SCLC compared with other types of lung cancer. p53 was expressed in 94.1% and survivin in 79.6% of the samples analyzed. CONCLUSION: The study calls attention to decreased expression of survivin, as opposed to p53, in small cell lung carcinoma.

Expression of anti-apoptotic protein survivin and tumor suppressor p53 protein in patients with pulmonary carcinoma.

BACKGROUND: Survivin is one of the inhibitors of the apoptosis gene family that has been implicated in both inhibition of apoptosis and mitosis regulation. p53 is one of the tumor suppressor genes; prevents tumor formation through cell cycle blocking and eliminates damaged cells via activation of apoptosis. OBJECTIVE: To investigate the possible regulation of survivin by p53, we examined the expression of both proteins in 67 patients with diagnosed lung cancer using immunohistochemical visualization. RESULTS: Survivin was predominantly expressed in both nucleus and cytoplasm, whereas p53 was expressed in the nucleus. There was a negative correlation between survivin and p53 expression. A decreased intensity of expression and fewer cells positive for survivin in small cell lung cancer in comparison with other lung cancer types were detected. There was no significant difference in the intensity of expression and the number of cells positive for p53 between small cell and non-small cell lung cancer types. CONCLUSION: The present study suggests that survivin expression, as opposed to that of p53, is decreased in small cell lung cancer, which may differentiate this cancer from other lung cancer types other types.

Pneumococcal vaccination--current situation and perspectives.

The authors carried out a survey in outpatient and hospitalised patients with risk factors for invasive pneumococcal disease in a tertiary-care medical faculty affiliated hospital. Data were collected by individual interviews and verified against the medical records of all addressed patients. The authors also attempted to discover the attitude of general practitioners (GPs) from 2 Slovak districts towards the pneumococcal vaccine by means of an anonymous questionnaire. Out of the total of 154 addressed patients, 128 (83.1%) had at least one risk factor for acquiring invasive pneumococcal disease. However, only 8 (6.3%) of them had ever been administered pneumococcal vaccine. Out of 34 hospitalised patients with at least one risk factor 82.4 % had not received any pneumococcal vaccination in the past. When subdivided according to age and risk factors (chronic respiratory, cardiovascular, uropoetic, metabolic, immunne system disorders, asplenia), vaccination coverage in all groups was very low, ranging between --9.3%. In an anonymous questionnaire 74 (94.9%) out of 77 surveyed GPs referred to a lack of information on the polysaccharide pneumococcal vaccine and 22 (28.2%) expressed their general distrust towards vaccination of any kind. The main role in increasing the disturbingly low pneumococcal vaccination coverage lies in the hands of medical professionals, especially GPs who should inform their patients about the possibility of a free vaccine and who should make an effort to explain to their patients the benefit of pneumococcal vaccination. (Tab. 4, Reft 9.)

Tobacco control and the role of the medical community in the Slovak Republic.

The Slovak Republic (SR) is located in central Europe and has a population of about 5.4 million. Epidemiological data indicate that trends in smoking prevalence and incidence of lung cancer have not shown any tendency to decrease in the SR. Surveys of Martin residents and of medical students at Comenius University provided important data on many aspects of cigarette smoking and tobacco dependence and served as a basis for planning and implementing focused tobacco control activities at the regional and national levels. The activities were focused not only on the Slovak public but also the medical community. With assistance from international organizations, Slovak doctors are learning to take direct responsibility for treatment and prevention and also a public responsibility to influence governmental policies. As a result, tobacco control activities in the SR enjoy collaboration between different agencies, community participation and personal involvement of health professionals.

Pharmacotherapy in smoking cessation.

The authors reviewed literature on nicotine replacement therapy and bupropion in smoking cessation. Nicotine replacement therapy increases the quit rate in smoking cessation; however, its efficacy is influenced by numerous factors. Bupropion, particularly combined with nicotine replacement therapy, reaches even higher efficacy. Behavioural therapy as well as individualized approach during the cessation process are beneficial. Beside from this, these agents help to avoid excessive weight gain after quitting. If properly used, they have minimal side effects, and, if not contraindicated, they should be included into standard smoking cessation programs. (Ref. 74.)

Spectra of the voluntary first cough sounds.

The voluntary cough sounds recorded according to Korpas and Sadlonova-Korpasova were sampled at a frequency of 20.000Hz and spectra of six consecutive windows of 50ms were estimated. To digitize signals an autotrigger mode was used. The subjects were healthy volunteers as well as patients with chronic bronchitis, asthma, bronchial carcinoma (growing intraluminarly in the 1st or in the 2nd or in the 3rd order bronchi), emphysema, laryngeal nerve paralyzis or laryngotomy. The duration of averaged cough sounds of patients was longer than that of healthy volunteers. The mean power of the spectra in the successive windows showed different patterns in the same group. In the third window of healthy volunteers (0.10 s-0.15 s) a high modulus broad bandwidth (between 1-2 kHz) spectrum was found which was considered as a bronchial "flute", and was probably related to the lowest resistance as well as to the velocity of airflow of cough manoeuvre. This pattern appeared with a delay and/or it was changed in the diseased groups compared to the healthy volunteers. Due to this delay, the spectra of the fifth window (0.20 s-0.25 s) showed somewhat higher harmonics (400-800 Hz) in the patients with chronic obstructive pulmonary diseases (COPD), carcinoma and laryngeal nerve paralyzis than in healthy volunteers. In emphysematous patients in the first (0.00-0.05 s), in the third (0.10-0.15 s) and in the fifth (0.20-0.25 s) windows the fundamental frequency was low (156-176 Hz) compared to that of the other groups. The paralyzed vocal cords functioning as an added resistance to the expiratory effort caused a phase-shift in the cough patterns, similarly to that seen in COPD patients. Due to the cannula, the spectra of patients having laryngotomy had a lot of high harmonics. They also had peaks nearly identical to that of bronchitic patients because they suffered from serious chronic bronchitis. It was found that by examination the cough spectra of series of voluntary cough sound signals it was possible to distinguish healthy volunteers from patients. This examination would therefore be useful for screening of bronchial diseases.

[Levels of alpha 1-antitrypsin in the blood of patients with chronic bronchitis]. / Hladiny alfa 1-antitrypsínu v sére chorých na chronickú bronchitídu.

Serum levels of alpha 1-antitrypsin were studied in 80 patients with chronic bronchitis. As a manifestation of the inflammatory response, nonsignificant increase was recorded compared to the group of healthy subjects. In discordance with literary data, no significant differences were found between bronchitics smokers and non-smokers. In 5 patients (6.2%), alpha 1-antitrypsin serum levels were below the lower limit of the reference range. The patients complained of cough, expectoration, and dyspnea. As a preventive measure, it is recommended to determine serum alpha 1-antitrypsin levels in smokers before they take up a job in a dusty environment and in bronchitics before inhalation treatment with proteolytic enzymes is administered. In alpha 1-antitrypsin deficit the value of substitution therapy in patients with emphysema is being emphasized.