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).

Gene polymorphisms of biotransforming enzymes (GSTs) and their association with lung cancer in the Slovakian population.

OBJECTIVE: The aim of present study was to present the results of a case-control study focused on genetic polymorphisms of selected Phase II metabolizing enzymes (GSTM1, T1, and P1) and to investigate the association of these polymorphisms with lung cancer risk in the Slovakian population. MATERIAL AND METHODS: The study encompassed 160 lung cancer cases and 220 controls. DNA was extracted from peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1 enzymes were determined by PCR-based methods. We determined the genotype distribution of all these genes and their combinations. The association between specific genotypes and the development of lung cancer were examined using logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: We found that the GSTM1 null genotype (OR=1.6; 95% CI=1.03-2.4; chi(2)=4.08, and P=0.04) was associated with elevated risk. A significant correlation also was found for the combined genotypes of GSTM1 null and GSTP1 Ile/Val and Val/Val (OR=2.01; 95% CI=1.1-6.1; chi(2)=3.6, and P=0.02) and GSTM1 null and GSTT1 positive (OR=2.00; 95% CI=1.2-3.2; chi(2)=7.3, and P=0.006). CONCLUSIONS: We conclude that the genotype of metabolizing enzymes and allelic combinations underscore the risk for lung cancer. Individual risk assessment may be further improved by increasing the number of polymorphisms studied and combining them with the traditional epidemiological risk factor.

[Radiation protective quality of spacesuit "Orlan-M" during extravehicular activities on the International Space Station].

Sampling irradiation of spacesuit "Orlan-M" allowed construction of a simulation model of the spacesuit shielding function for critical body organs. The critical organs self-shielding model is a Russian standard anthropomorphic phantom. Radiation protective quality of the spacesuit was assessed by calculating the dose attenuation rates for several critical body organs of an ISS crewmember implementing EVA. These calculations are intended for more accurate assessment of radiation risk to the ISS crews donning "Orlan-M" in near-Earth orbits.

[Effect of loading suit "Penguin" on human metabolism during movements]. / Vliianie profilakticheskogo nagruzochnogo kostiuma "Pingvin" na metabolizm cheloveka pri dvizheniiakh.

Additional energy expenses due to stretching of the elastic elements of anti-loading suit (ALS) "Penguin" as a whole (shoulders-feet) or only its lower part (waist-feet) in the course of cyclic leg movements were measured in five female and five male volunteers. ALS design enabled tensometric monitoring of efforts applied to specific elastic elements, and total efforts applied to the shoulder or pelvic girdles separately. Energy spend were determined with the indirect calorimetric techniques from the data of the expired air analysis. Registered were electromyograms of m. longus spinae, femoral extensor (m. biceps femoris) and femoral flexor (m. rectus femoris), and m. gastrocnemius. On the first stage, bicycle ergometer was pedaled w/o loading with a frequency of 60 cycles/min. The next stage included testing by incremental loading in which pedaling ceased at the pulse rate of 150/min. Results of the experiments that did not require stretching elastic parts of the suit and in which the total strain effort made up 20 to 25 kg and 15 to 16 kg by males and females, respectively, were compared. It was ascertained that ALS enhanced metabolism during motion by 20 to 30%; however, there was no significant difference in energy expenses when loaded by the whole suit or only its lower part.

[Prevention of respiratory muscles deconditioning and deterioration of aerobic working capacity in prolonged weightlessness and hypokinesia]. / Profilaktika detrenirovannosti dykhatel'nykh myshts i snizhenie aérobnoi rabotosposobnosti v usloviiakh dlitel'noi nevesomosti i gipokinezii.

According to the previous study [2], simulation of the physiological effects of weightlessness leads to deconditioning of the respiratory muscles which, in its turn, may be a factor impacting the aerobic working capacity. In the present work the experimental findings laid the basis for a physiological concept for medical/engineering requirements to countermeasures against deconditioning of the respiratory muscles, designing and laboratory and physiological testing of a prototype of training loading vest Elastik-R. The vest was shown to enhance speed and force qualities of the respiratory muscles in training athletes, to improve ventilation and gas-exchange functions of the lung, and to increase physical performance and aerobic capacity. Recommendations on utilization of the Elastik-R vest during space flight have been issued.

[Changes in the basic indices of human hemodynamics in lower body compression using an anti-G suit]. / Izmeneniia osnovnykh pokazatelei gemodinamiki cheloveka pri obzhatii nizhnei chasti tela protivoperegruzochnym kostiumom.

Changes in cardiovascular parameters of test subjects wearing anti-G suits were studied under static conditions. The study was carried out, using methods of radioactive label dilution, radiocardiography and tetrapolar rheography. The study demonstrated the highest level of physiological reactions within short transition periods after inflation and deflation of suit bladders.

[Several hemodynamic indices during human breathing of oxygen under excess pressure]. / Nekotorye pokazateli gemodinamiki pri dykhanii cheloveka kislorodom pod izbytochnym davleniem.

The paper gives the experimental findings on the pattern and value of circulation changes in ten test subjects exposed to oxygen breathing at positive pressure of 20 mm Hg. The major parameters of central circulation were registered by the method of radioactive label (I131) dilution. During the exposure the test subjects showed an average 27% decrease in the cardiac output as compared with the control level. The test subjects who were pretrained to the exposure displayed a smaller reduction of cardiac output. It is suggested that the circulation changes found under the experimental conditions were mainly induced by peripheral changes rather than by the cardiac function. It is concluded that the reduction of cardiac output is associated with a decrease of the venous return to the heart caused by the diminished circulating blood volume and by the increased total peripheral resistance.