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Biomedical subjects

Vladimir Bencko

Publications and source records attributed to Vladimir Bencko.

16 recordsLinked to original sources
PubMed2007

Esophageal cancer in Central and Eastern Europe: tobacco and alcohol.

Esophageal cancer mortality rates in Central and Eastern Europe have been increasing steadily and are expected to increase further in the future. To evaluate the role of risk factors for esophageal cancer in this population, a multicenter study was conducted, with investigation of tobacco and alcohol as one of the principal aims. We have included 192 squamous cell carcinoma (SCC) and 35 adenocarcinoma cases of the esophagus diagnosed at designated hospitals in 5 centers from Romania, Russia, the Czech Republic and Poland. Controls were frequency matched from patients in the same hospital as the cases (n=1,114). Our results showed that the risk of esophageal SCC may be increased by approximately 7-fold for current smokers (OR=7.41, 95% CI 3.98-13.79) and by 3-fold for ever alcohol drinkers (OR=2.86, 95% CI 1.06-7.74). Dose-response relations were evident for both the frequency and duration of tobacco and of alcohol on the risk of esophageal SCC. Risk estimates for tobacco smoking were highest for lower esophageal SCCs, while risk estimates for alcohol drinking were highest for upper esophageal SCCs; though differences were not statistically significant. For adenocarcinoma of the esophagus, our results suggested a more modest increase in risk because of tobacco smoking than that for SCC of the esophagus and no association with alcohol consumption, although our sample size was small. A synergistic interaction between tobacco and alcohol was observed for the risk of esophageal SCC, highlighting the importance of both factors for esophageal cancers in Central and Eastern Europe.

Adenocarcinoma↗
PubMed2007

Occupational exposure to crystalline silica and risk of lung cancer: a multicenter case-control study in Europe.

BACKGROUND: The role of crystalline silica dust as a possible cause of lung cancer has been controversial. Relatively few large community-based studies have been conducted to investigate the lung cancer risk from exposure to silica at low levels, taking into account potential confounding factors. METHODS: Detailed lifestyle and occupational information were collected from 2852 newly diagnosed cases of lung cancer and 3104 controls between 1998 and 2002 in 7 European countries. For each job held, local experts assessed the probability, intensity, and duration of silica exposure. RESULTS: Occupational exposure to crystalline silica was associated with an increased risk of lung cancer (odds ratio = 1.37; 95% confidence interval = 1.14-1.65). This risk was most apparent for the upper tertile of cumulative exposure (OR = 2.08; 95% CI = 1.49-2.90; P for trend <0.0001), duration of exposure (1.73; 1.26-2.39; P for trend = 0.0001) and weighted duration of exposure (1.88; 1.35-2.61; P for trend <0.0001). We did not observe any interaction beyond a multiplicative model between tobacco smoking and silica exposure. CONCLUSIONS: Our results support the hypothesis that silica is an important risk factor for lung cancer. This risk could not be explained by exposure to other occupational carcinogens or smoking, and it was present for the main histologic types of lung cancer, different sources of silica exposure, and different industrial settings.

Adenocarcinoma↗
PubMed2006

DNA repair and cell cycle control genes and the risk of young-onset lung cancer.

Exposure to tobacco smoke and to mutagenic xenobiotics can cause various types of DNA damage in lung cells, which, if not corrected by DNA repair systems, may lead to deregulation of the cell cycle and, ultimately, to cancer. Genetic variation could thus be an important factor in determining susceptibility to tobacco-induced lung cancer with genetic susceptibility playing a larger role in young-onset cases compared with that in the general population. We have therefore studied 102 single-nucleotide polymorphisms (SNP) in 34 key DNA repair and cell cycle control genes in 299 lung cancer cases diagnosed before the age of 50 years and 317 controls from six countries of Central and Eastern Europe. We have found no association of lung cancer risk with polymorphisms in genes related to cell cycle control, single-strand/double-strand break repair, or base excision repair. Significant associations (P < 0.05) were found with polymorphisms in genes involved in DNA damage sensing (ATM) and, interestingly, in four genes encoding proteins involved in mismatch repair (LIG1, LIG3, MLH1, and MSH6). The strongest associations were observed with heterozygote carriers of LIG1 -7C>T [odds ratio (OR), 1.73; 95% confidence interval (95% CI), 1.13-2.64] and homozygote carriers of LIG3 rs1052536 (OR, 2.05; 95% CI, 1.25-3.38). Consideration of the relatively large number of markers assessed diminishes the significance of these findings; thus, these SNPs should be considered promising candidates for further investigation in other independent populations.

Adult↗
PubMed2006

Occupational exposure to asbestos and man-made vitreous fibres and risk of lung cancer: a multicentre case-control study in Europe.

OBJECTIVES: To investigate the contribution of occupational exposure to asbestos and man-made vitreous fibres (MMVF) to lung cancer in high-risk populations in Europe. METHODS: A multicentre case-control study was conducted in six Central and Eastern European countries and the UK, during the period 1998-2002. Comprehensive occupational and sociodemographic information was collected from 2205 newly diagnosed male lung cancer cases and 2305 frequency matched controls. Odds ratios (OR) of lung cancer were calculated after adjusting for other relevant occupational exposures and tobacco smoking. RESULTS: The OR for asbestos exposure was 0.92 (95% CI 0.73 to 1.15) in Central and Eastern Europe and 1.85 (95% CI 1.07 to 3.21) in the UK. Similar ORs were found for exposure to amphibole asbestos. The OR for MMVF exposure was 1.23 (95% CI 0.88 to 1.71) with no evidence of heterogeneity by country. No synergistic effect either between asbestos and MMVF or between any of them and smoking was found. CONCLUSION: In this large community-based study occupational exposure to asbestos and MMVF does not appear to contribute to the lung cancer burden in men in Central and Eastern Europe. In contrast, in the UK the authors found an increased risk of lung cancer following exposure to asbestos. Differences in fibre type and circumstances of exposure may explain these results.

Asbestos↗
PubMed2006

High cumulative risk of lung cancer death among smokers and nonsmokers in Central and Eastern Europe.

The authors have calculated cumulative risks of lung cancer from a case-control study conducted between 1998 and 2002 involving 2,633 lung cancer cases and 2,884 controls in Hungary, Poland, the Czech Republic, Slovakia, Romania, and Russia. The odds ratios for smoking history were combined with national lung cancer mortality rates to obtain the cumulative risk of lung cancer. The cumulative risk of death from lung cancer by the age of 75 years among current male smokers was 14.6% in Romania and Russia and 15.8% in Poland, similar to levels reported in Western Europe, although higher risks were found in the Czech Republic (19.8%), Hungary (21.9%), and Slovakia (28.2%). Cumulative risks of lung cancer death among never smokers of over 1% were observed in Hungary among both men and women and among men in Poland. The effect of quitting smoking on the lifetime cumulative risk was substantial, with between 67% and 83% of lung cancer risk among men being avoided by quitting before the age of 50 years. This substantial reduction in risk among former smokers confirms that lung cancer mortality in Central Europe over the next three decades will be determined by the extent to which current smokers can successfully quit smoking.

Adult↗
PubMed2006

Sequence variants in cell cycle control pathway, X-ray exposure, and lung cancer risk: a multicenter case-control study in Central Europe.

Exposure to ionizing radiation (IR) results in various types of DNA damage and is a suspected cause of lung cancer. An essential cellular machinery against DNA damage is cell cycle control, which is regulated by several genes, including TP53, CCND1, and CDKN2A. Therefore, we hypothesized that the genetic variants in these three genes influence the predisposition of lung cancer (i.e., CCND1 G870A, CDKN2A Ala(148)Thr, TP53 Arg(72)Pro, and 16-bp repeat in intron 3) and that the effect of X-ray on lung cancer risk can be modified by the presence of these genetic variations. The study was conducted in 15 centers in 6 countries of Central Europe between 1998 and 2002. A total of 2,238 cases and 2,289 controls were recruited and provided DNA samples. Cases with positive family history were analyzed separately. The joint effect of X-ray and previous risk genotypes was assessed, and modification by sequence variants on X-ray dose-response relationship with lung cancer risk was evaluated. We found an overall effect of TP53 intron 3 16-bp repeats [odds ratio (OR), 1.99; 95% confidence interval (95% CI), 1.27-3.13], which was stronger among cases with family history of lung cancer (OR, 2.98; 95% CI, 1.29-6.87). In addition, our results suggested an interaction that was greater than multiplicativity between TP53 intron 3 16-bp repeats and multiple X-ray exposures (interaction OR, 5.69; 95% CI, 1.33-24.3). We did not observe a main effect of CCND1 G870A polymorphism; however, the dose-response relationship between lung cancer risk and X-ray exposures was modified by CCND1 genotype with no risk from X-ray exposures among subjects who carried G/G genotype, intermediate risk [trend OR for X-ray, 1.16; 95% CI, 1.05-1.27) among subjects with G/A genotype, and highest risk [trend OR for X-ray, 1.29; 95% CI, 1.12-1.49) among subjects with A/A genotype. Sequence variants in cell cycle control pathway may increase the risk of lung cancer and modify the risk conferred by multiple X-ray exposures. However, a definite conclusion can only be drawn on replication by different studies among individuals who are highly exposed to IR.

Case-Control Studies↗
PubMed2006

Lung cancer risk and occupational exposure to meat and live animals.

An increased risk of lung cancer has been reported for butchers and meat workers in several cohort studies, although confounding from tobacco smoking could not be ruled out in any of these studies. These exposures, as well as a potential risk associated with contact with live animals, are addressed here in a large case-control study with full adjustment for smoking. More than 5,900 subjects were included in a case-control study conducted in 7 European countries. For each job they employed local experts who assessed the exposure to a number of occupational agents, including (i) meat aerosols and (ii) live animals, on the basis of detailed occupational questionnaires. Information on tobacco consumption and other risk factors was also collected. A small increased risk of lung cancer was observed with exposure to meat aerosols, after adjusting for smoking, (odds ratio (OR)=1.27, 95% confidence interval (CI): 0.92, 1.75), which was most apparent for the upper tertile of cumulative exposure (OR=1.73, 95% CI: 1.03, 2.92). A similar overall effect was observed for exposure to live animals, with an increased risk observed for a high frequency of exposure, (OR=1.69, 95% CI: 1.21, 2.36) and a high intensity of exposure, (OR=1.85, 95% CI: 1.16, 2.94), with significant trends for increasing frequency (p=0.012), intensity (p=0.015) and cumulative exposure (p=0.024). In conclusion, this study provides evidence for an association between exposure to meat aerosols and lung cancer apparent in the highest tertile of exposure. The authors identified a more consistent association with exposure to live animals.

Adult↗
PubMed2006

Lung cancer and occupation in nonsmokers: a multicenter case-control study in Europe.

BACKGROUND: Tobacco smoking is the main cause for lung cancer worldwide, making it difficult to examine the carcinogenic role of other risk factors because of possible confounding by smoking. Therefore, the present study aimed to investigate the association between lung cancer and occupation independent of smoking. METHODS: A case-control study of lung cancer was carried out between March 1998 and January 2002 in 16 centers from 7 European countries, including 223 never-smoking cases and 1039 controls. Information on lifestyle and occupation was obtained through detailed questionnaires. Job and industries were classified as entailing exposure to known or suspected carcinogens; in addition, expert assessment provided exposure estimates to specific agents. RESULTS: The odds ratio of lung cancer among women employed for more than 12 years in suspected high-risk occupations was 1.75 (95% confidence interval = 0.63-4.85). A comparable increase in risk was not detected for employment in established high-risk occupations or among men. Increased risk of lung cancer was suggested among individuals exposed to nonferrous metal dust and fumes, crystalline silica, and organic solvents. CONCLUSION: Occupations were found to play a limited role in lung cancer risk among never-smokers. Jobs entailing exposure to suspected lung carcinogens should receive priority in future studies among women. Nonferrous metal dust and fumes and silica may exert a carcinogenic effect independently from smoking.

Case-Control Studies↗
PubMed2006

Evidence for an important role of alcohol- and aldehyde-metabolizing genes in cancers of the upper aerodigestive tract.

BACKGROUND: Incidence and mortality rates of upper aerodigestive tract cancers in Central Europe are among the highest in the world and have increased substantially in recent years. This increase is likely to be due to patterns of alcohol and tobacco consumption. Genetic susceptibility to upper aerodigestive tract cancer in relation to such exposures is an important aspect that should be investigated among populations in this region. METHODS: A multicenter case-control study comprising 811 upper aerodigestive tract cancer cases and 1,083 controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia), Banska Bystrika (Slovakia), and Olomouc and Prague (Czech Republic). We analyzed six SNPs in three genes related to ethanol metabolism: alcohol dehydrogenase 1B and 1C (ADH1B, ADH1C) and aldehyde dehydrogenase 2 (ALDH2). RESULTS: The ADH1B histidine allele at codon 48 was associated with a decreased risk of upper aerodigestive tract cancer; odds ratios (OR) were 0.36 [95% confidence interval (95% CI), 0.17-0.77] for medium/heavy drinkers and 0.57 (95% CI, 0.36-0.91) for never/light drinkers. Moderately increased risks were observed for the ADH1C (350)Val allele (OR, 1.19; 95% CI, 0.98-1.55) and ADH1C (272)Gln allele (OR, 1.24; 95% CI, 0.98-1.55). Medium/heavy drinkers who were heterozygous or homozygous at ALDH2 nucleotide position 248 were at a significantly increased risk of upper aerodigestive tract cancer (OR, 1.76; 95% CI, 1.13-2.75; OR, 5.79; 95% CI, 1.49-22.5, respectively), with a significant dose response for carrying variant alleles (P = 0.0007). Similar results were observed for the ALDH2 +82A>G and ALDH2 -261C>T polymorphisms. When results were analyzed by subsite, strong main effects were observed for squamous cell carcinoma of the esophagus for all six variants. Among the 30% of the population who were carriers of at least one ALDH2 variant, the attributable fraction among carriers (AF(c)) was 24.2% (5.7-38.3%) for all upper aerodigestive tract cancers, increasing to 58.7% (41.2-71.0%) for esophageal cancer. Among carriers who drank alcohol at least thrice to four times a week, the AF(c) for having at least one ALDH2 variant was 49% (21.3-66.8%) for all upper aerodigestive tract cancers, increasing to 68.9% (42.9-83.1%) for esophageal cancer. CONCLUSIONS: Polymorphisms in the ADH1B and ALDH2 genes are associated with upper aerodigestive tract cancer in Central European populations and interact substantially with alcohol consumption.

Adult↗
PubMed2005

Is the risk of lung cancer reduced among eczema patients?

Persons with a history of eczema have been shown to have a reduced risk of lung cancer, but the evidence has been inconclusive because of the small size of previous studies and their limited ability to control for confounding by smoking. The objective of this study was to determine the role of eczema in relation to lung cancer while overcoming the limitations of previous investigations. Study subjects included 2,854 cases and 3,116 population and hospital controls recruited during 1998-2001 from 16 areas in the Czech Republic, Hungary, Poland, Romania, Russia, Slovakia, and the United Kingdom. Odds ratios were calculated for self-reported history of eczema via multivariate logistic regression modeling. The odds ratio for a history of eczema was 0.61 (95% confidence interval: 0.48, 0.76) after control for age, sex, study center, and cumulative tobacco smoking. There was no heterogeneity in the results by sex or age at onset of eczema. Subjects reporting use of medication for eczema had a lower odds ratio than subjects not reporting such use. This study provides further evidence for an inverse association between history of eczema and lung cancer risk, which is unlikely to be due to chance, bias, or confounding.

Adult↗
PubMed2005

Occupational X-ray examinations and lung cancer risk.

Occupational X-ray examination programs have been conducted in many countries to screen for occupational and nonoccupational respiratory diseases, resulting in widespread exposure to X-radiation. We conducted a multicentre case-control study of lung cancer in the Czech Republic, Hungary, Poland, Romania, Russia and Slovakia, including 2,589 cases and 2,859 controls enrolled during 1998-2002. We collected detailed information on occupational X-ray examinations, occupations and tobacco smoking. We calculated odds ratios of lung cancer via multiple logistic regression after adjustment for age, sex, center and tobacco smoking. Among controls 24.9% reported no X-ray examination, 62.9% reported 1-30 examinations and 12.2% reported more than 30 examinations. When we chose individuals with no examination as the reference group, the odds ratios of lung cancer were 1.21 (95% confidence interval [CI] 0.99-1.48), 1.33 (95% CI 1.08-1.64), 1.49 (95% CI 1.18-1.87), 1.52 (95% CI 1.17-1.99) and 2.15 (95% CI 1.50-3.08) for 1-10, 11-20, 21-30, 31-40 and more than 40 examinations, respectively (p-value of test for linear trend <0.0001). The association between X-ray examinations and lung cancer risk was strong in countries with low prevalence of exposure and absent in countries with high prevalence of exposure. Odds ratios for X-ray examinations were lower among smokers than among nonsmokers. The magnitude of the increased risk observed is higher than expected on the basis of other studies of radiation-exposed populations. Although the association we detected between X-ray examinations and lung cancer risk may reflect a carcinogenic effect of repeated exposure to low-level ionizing radiation, reporting bias and particularly uncontrolled confounding by occupational exposure to carcinogens are also likely explanations of the results.

Adult↗
PubMed2005

Large-scale investigation of base excision repair genetic polymorphisms and lung cancer risk in a multicenter study.

BACKGROUND: Base excision repair (BER) is a highly conserved essential mechanism for maintaining genome integrity. We examined associations among four well-characterized polymorphisms of BER genes (OGG1 Ser326Cys, XRCC1 Arg194Trp, XRCC1 Arg280His, and XRCC1 Arg399Gln) and lung cancer risk. METHODS: A total of 2188 patients with lung cancer and 2198 control subjects without lung cancer recruited at 15 centers in six Eastern European countries from February 1998 to October 2002 provided DNA samples for genotype analysis. Genetic polymorphisms were analyzed by the fluorescence 5' exonuclease and Amplifluor assays. Unconditional multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We estimated the false-positive reporting probability (FPRP) for our results by incorporating a range of prior probabilities that specific polymorphisms are associated with lung cancer risk. All statistical tests were two-sided. RESULTS: The overall odds ratio for lung cancer among those with the OGG1 Cys/Cys genotype compared with those with the OGG1 Ser/Ser genotype was 1.34 (95% CI = 0.95 to 1.88); the association was most prominent for adenocarcinoma risk (OR = 1.66, 95% CI = 1.04 to 2.66). Overall, the XRCC1 polymorphisms were not associated with the risk of lung cancer. However, the XRCC1 Arg194Trp and Arg280His variants were each associated with a reduced risk of lung cancer among subjects in the highest quartile of pack-years of smoking compared with common allele homozygotes (ORs of 0.65 [95% CI = 0.46 to 0.93] and 0.56 [95% CI = 0.36 to 0.86], respectively). The associations between the OGG1 Cys/Cys genotype and adenocarcinoma risk and between XRCC1 Arg194Trp polymorphism and lung cancer risk among heavy smokers remained robust given prior probabilities of 25% (FPRP = 0.238) and 10% (FPRP = 0.276), respectively. CONCLUSIONS: Our results do not support a major independent role of BER gene polymorphisms in lung cancer risk. However, we cannot exclude the possibility that the OGG1 Ser326Cys and XRCC1 Arg194Trp polymorphisms play minor roles in lung carcinogenesis.

Adenocarcinoma↗
PubMed2002

Interference of CD95 expression on human lymphocytes.

The study presents the exogenous influence of cadmium in comparison with zinc on the apoptosis of human lymphocytes by CD95 expression and its kinetic changes. The salts of both metals were used in final concentrations of 20 microM in cell cultures with whole blood. The duration of cultivation was 18 and 90 hours. The expression of surface antigens was evaluated by flow cytometry with monoclonal antibodies. In cultures of not stimulated cells we found in average 51.54% CD95 positive lymphocytes. The kinetic study of untreated cells showed elevation after 18 hours of cultivation and a very low expression after 90 hours. The CD95 expression on lymphocytes in cell culture with cadmium and zinc was lower after 18 hours of cultivation than in untreated cells. After 90 hours cultivation we found low levels of CD95 expression on cells treated with cadmium and a great individual variability in the number of positive cells upon the influence of zinc.

Apoptosis↗
PubMedDate not supplied

Effect of cruciferous vegetables on lung cancer in patients stratified by genetic status: a mendelian randomisation approach.

Whether consumption of cruciferous vegetables protects against lung cancer is unclear, largely because of potential confounding factors. We therefore studied the role of cruciferous vegetables in lung cancer after stratifying by GSTM1 and GSTT1 status, two genes implicated in the elimination of isothiocyanates, the likely chemopreventative compound. In 2141 cases and 2168 controls, weekly consumption of cruciferous vegetables protected against lung cancer in those who were GSTM1 null (odds ratio=0.67, 95% CI 0.49-0.91), GSTT1 null (0.63, 0.37-1.07), or both (0.28, 0.11-0.67). No protective effect was seen in people who were both GSTM1 and GSTT1 positive (0.88, 0.65-1.21). Similar protective results were noted for consumption of cabbage and a combination of broccoli and brussels sprouts. These data provide strong evidence for a substantial protective effect of cruciferous vegetable consumption on lung cancer.

Case-Control Studies↗