Elena Kavcova

Structural chromosomal aberrations as potential risk markers in incident cancer patients

Epidemiological prospective studies have shown that increased chromosomal aberrations (CAs) in peripheral blood lymphocytes may predict cancer risk. Here, we report CAs in newly diagnosed 101 colorectal, 87 lung and 158 breast cancer patients and corresponding healthy controls. Strong differences in distributions of aberrant cells (ACs), CAs, chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) were observed in lung and breast cancer patients as compared to healthy controls. In colorectal cancer (CRC) patients, only CTAs were significantly elevated. Binary logistic regression, adjusted for main confounders, indicates that all the analysed cytogenetic parameters along with smoking were significantly associated with breast and lung cancer risks. Significant differences in terminal deletions between breast cancer patients and corresponding female controls were recorded (0.39 vs. 0.18; P ≤ 0.05). We did not find any association of CAs with TNM (tumor nodus metastasis) stages or histopathological grade in either cancer type. CAs were neither associated with additional tumor characteristics-invasivity, ductal and lobular character, estrogene/progesterone receptors in breast tumors nor with non-small/small cell and bronchogenic/pulmonary types of lung tumors. Our study demonstrates that CAs serve as a predictive marker for breast and lung cancer, whereas only CTAs were elevated in incident CRC patients.

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

ObjectiveWorkers 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.Materials and methods67 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.ResultsChromium 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.ConclusionThe study calls attention to decreased expression of survivin, as opposed to p53, in small cell lung carcinoma.

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.

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.

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

BackgroundSurvivin 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.ObjectiveTo 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.ResultsSurvivin 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.ConclusionThe 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.

Smoking habits and knowledge of its harmful effects among medical students in the Slovak Republic

Medical doctors should be the leaders in tobacco prevention activities. As role models for their patients and as helpers, leaders and activists, they are needed in campaigns to reduce smoking. We were interested in the smoking behaviour and attitudes towards smoking of Slovak medical students, who represent the next generation of medical doctors.