[EVALUATION OF THE CARCINOGENIC RISK OF LEAD IN THE COHORT STUDY OF MALE WORKERS OCCUPATIONALLY EXPOSED TO INORGANIC LEAD IN 27 MOSCOW PRINTING-HOUSES].

As millions of people worldwide are expoed to inorganic lead, both in the workplace and in general environment, its potential carcinogenicity is an important health problem. Although lead has been shown to be carcinogenic in laboratory animals, epidemiological studies have been inconclusive, and the relationship between lead and human cancer is still unclear. There were several limitations that complicated the analysis and evaluation of the carcinogenic potential of lead compounds. In particular, many of the cohort studies of lead and cancer, mostly among heavily lead-exposed workers, have been limited by a failure to identify and control for covariates, especially co-exposures to other metals such as arsenic, cadmium, and chromium, which have been shown to be carcinogenic. Most of the epidemiological studies unfortunately do not have data on dose-response. The scientific merit of our study is the virtual absence of confounding by other known carcinogens. Another advantage of our study is the presence of three occupational sub-cohorts with different levels and routes of lead exposure. Most previous studies have data on dose-response provided only by comparisons of exposed to unexposed persons. In summary, the results of this cohort study suggest that occupational exposure to lead may increase the risk of cancers of the pancreas, kidney and rectum. In conclusion, despite several limitations, the results of our study add to the evidence that carcinogenicity to humans may be an additional adverse health effect of lead.

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.

[Assessment of carcinogenic activity of industrial toxicants in occupational epidemiological surveys].

Evaluation of cancer morbidity and mortality from workplace exposure to industrial toxicants is a main avenue of research aimed to identify causes of human cancer. Many chemicals classified as carcinogens by International Agency for Cancer Research were first identified at workplaces. However, the value of these findings for the study of carcinogens in the occupational environment was compromised for a variety of reasons. A major methodological problem is to elucidate the cause-and effect relationship between inhomogeneous exposure to industrial pollution and cancer morbidity/mortality rates in different categories of workers. Another important problem in occupational epidemiology is the deficiency of data on the exposure level in women because reproductive organs are specific targets of certain chemicals and their carcinogenic effects are especially well apparent as gynecological diseases. Moreover gender-specific differences account for different risks and outcomes of apparently similar environmental exposure.

Combining two technologies for full genome sequencing of human.

At present, the new technologies of DNA sequencing are rapidly developing allowing quick and efficient characterisation of organisms at the level of the genome structure. In this study, the whole genome sequencing of a human (Russian man) was performed using two technologies currently present on the market - Sequencing by Oligonucleotide Ligation and Detection (SOLiD™) (Applied Biosystems) and sequencing technologies of molecular clusters using fluorescently labeled precursors (Illumina). The total number of generated data resulted in 108.3 billion base pairs (60.2 billion from Illumina technology and 48.1 billion from SOLiD technology). Statistics performed on reads generated by GAII and SOLiD showed that they covered 75% and 96% of the genome respectively. Short polymorphic regions were detected with comparable accuracy however, the absolute amount of them revealed by SOLiD was several times less than by GAII. Optimal algorithm for using the latest methods of sequencing was established for the analysis of individual human genomes. The study is the first Russian effort towards whole human genome sequencing.

Molecular epidemiology of cancer.

In this review the role of molecular markers for the assessment of individual exposure to carcinogenic agents was analyzed. Examples of the studies describing mutation patterns related to specific carcinogenic exposures are presented. The results of epidemiological studies of gene polymorphism and its role in the interaction between inheritance, environmental factors, and lifestyles are analyzed in detail. Adequate planning and performance of the epidemiological component of a study is a requirement for obtaining reproducible results reflecting molecular mechanisms of interest. Individual information on lifestyle factors (smoking, alcohol consumption, nutrition, physical activity, reproductive anamnesis) and environmental factors (occupational activity and carcinogen load at workplace), which influence not only the risk of developing cancer, but also the molecular features of a tumor, is crucial for adequate analysis and proper assessment of the results.

[Evaluation of potential carcinogenic hazards of lead and lead compounds].

A considerable percentage of Russian population, as well as in other countries, are at risk of exposure to lead as an industrial highly toxic hazard. It is notorious for polytropic influence, high stability both in human body and environment; it has a cumulative effect and a possible distant after-effect. An IARC working group carried out an evaluation of the data on lead carcinogenicity in industrial cohorts and found no suspicious risks. Inorganic lead compounds were classified as "probably carcinogenic to humans" (group 2B). Later on, the IARC Working Group (2004) referred those substances to group 2A (carcinogenic to humans).

[Risk factors of laryngeal cancer in Central and Eastern Europe].

A case-control epidemiologic study in squamous-cell carcinoma of the larynx (LC) vs. smoking was carried out. Although no independent influence of drinking was found, the synergetic effect of the two habits potentiated the carcinogenic impact. Approximately 87% of LC cases are attributable to tobacco use in Central and Eastern Europe. Occupational exposure to coal dust is regarded as a possible cause.

[Carcinogenic components of smokeless tobacco and tobacco-free cigarettes].

The investigation deals with an assessment of carcinogenicity and mutagenicity of samples of smokeless tobacco now on the Russian market as well as ash from alternative cigarettes made of aromatic herbs. Our data showed that the levels of polycyclic aromatic hydrocarbons, volatile and tobacco-specific N-nitrosoamines complied with the standards in the producer-countries. Smokeless tobacco extracts failed to show (Ames) any mutagenic effects such as the "read-out frame shift" or "base-pair replacement" patterns. No tobacco-specific N-nitrosoamines were identified in herbal cigarettes. However, polycyclic aromatic hydrocarbons and volatile N-nitrosoamines content appeared to be identical to that of tobacco. Herbal cigarette smoke extracts mutagenicity induced by side-effects of carcinogenic substances was of similar magnitude as well.

[Low-deuterium water effect on transplantable tumors].

Such models of transplantable tumors as Lewis sarcoma, uterine sarcoma-322 and uterine carcinoma-5 were used to study possible inhibitory effect by low-deuterium water. Such water was given to experimental animals (20 mice in each group). Controls (30 in each group) received tap water with standard deuterium concentrations. Low-deuterium water treatment resulted in significant inhibitory effect on volume of all tumor patterns concerned: it delayed nodule formation at transplantation site. However, no increase in survival time was obtained.

[Methodological basics of prognosticating the life expectancy of population in big cities]. / Metodicheskie osnovy opredeleniia ozhidaemoi prodolzhitel'nosti zhizni naseleniia bol'shikh gorodov.

The reasons of high mortality and of low life expectancy among Russian citizens as well as their sharp fluctuations observed in the 90-ies were explained differently by researchers, however, no attempt was made to analyze the impact made by a huge inflow of immigrant from the republics of the former USSR and "close abroad" in any case studies. In this paper we point at the fact that the mortality statistics and life expectancy in Moscow were influenced, at least for as long as 12 years, by a systemic error, which made the mortality index higher and the life expectancy lower, among Muscovites, due to overestimates of the absolute number of died Muscovites and to underestimates of the city residents. The 2001 life expectancy of men and women in Moscow calculated on the basis of data, from which non-residents who died in the capital were deleted, was 64.7 and 75.0, respectively, but not 61.7 and 73.5 as represented by the official statistics. The maximum negative effect of death cases of non-residents exerted on the life expectancy coincides with the overall mortality peak value in Moscow: life expectancy of Muscovites for 1994 estimated without accounting of the mortality rate for non-residents turned out to be 3.2 years higher for men and 1.5 years higher for women. Supposedly, the Russian mortality statistics is not nation-wide in line with the actual state of affairs. However, the influence of the discussed systemic error in Russia's regions can be expected to be less pronounced since the level of immigration in Moscow is most probably by far higher.

[Etiological aspects of occupational cancer in printing industry]. / Etiologicheskie aspekty professional'nogo raka v poligraficheskoi promyshlennosti.

Research of oncology lethality from workplace exposures is one of the most effective approaches to studying the etiology of malignant neoplasms. However, certain problems of methodology compromise the informative value of such research whose purpose is to identify the carcinogens. Addition of data on morbidity and lethality in heterogeneous industrial categories, whose typical feature are inhomogeneous exposures, is a major methodological problem. The fact that the studied occupational populations are limited to male subjects is another important problem. The most adequate epidemiological study projects were analyzed and compared with the results of our own case study, which dealt, for the first time in the history of our country, with investigating the lethality causes of 1552 males and 3473 females occupied as compositors, printers and bookbinders at two major printing enterprises in the city of Moscow. According to the authors, an exposure to polycyclic aromatic hydrocarbons, e.g. benzopirin, could be a reliably higher risk of mortality of melanoma and of ovarian cancer among female press operators. With regard for experimental and epidemiological research, the authors believe it appropriate to put forward the below hypothesis: a many-year exposure to minimal quantities of asbestos contained in the paper dust was the key trigger inducing the malignant mesothelioma and ovarian cancer in bookbinders and printers.

[Consideration of the deuterium-free water supply to an expedition to Mars]. / Vozmozhnost' ispol'zovaniia bezdeiterievoi vosy v marsianskoi ékspeditsii.

Interplanetary missions, including to Mars, will put crews into severe radiation conditions. Search for methods of reducing the risk of radiation-induced cancer is of the top priority in preparation for the mission to Mars. One of the options is designing life support systems that will generate water with low content of the stable hydrogen isotope (deuterium) to be consumed by crewmembers. Preliminary investigations have shown that a decrease of the deuterium fraction by 65% does impart to water certain anti-cancer properties. Therefore, drinking deuterium-free water has the potential to reduce the risk of cancer consequent to the extreme radiation exposure of the Martian crew.

[Smoking: the main cause of high mortality rate among Russian population]. / Kurenie -- osnovnaia prichina vysokoi smertnosti rossiian.

Mortality rates in Russia are very high as compared to those in other developed countries, particularly among men. A series of hypotheses associating heavy drinking and social and economic stresses of the transition period with drastic increases in mortality rates in Russia in the mid-1990s have been generated. However, the hypotheses are under analytical study on an individual level. A case control study was carried out to investigate the association of mortality due to smoking, alcoholic consumption, and a variety of socioeconomic indices. A total of 13,079 individuals who died in 1990-1999 were identified during a populational survey of 90,147 families in four Russian cities: Barnaul, Tomsk, Tyumen, and Vladivostok. Data on lifestyle habits, such as smoking, alcohol consumption, and some socioeconomic characteristics of the deceased were obtained from questionnaire surveys with proxy respondents (wives, husbands, etc.). Proportional mortality analyses were carried out. Controls were selected from those who died from non-smoking-related causes. A statistically significant association was established between smoking and the risk of death due to cancers of the lung, mouth, pharynx, larynx, esophagus, stomach, and urinary bladder. There was also a dose-response relationship of the numbers of cigarettes smoked to the risk of cancers at these sites. Smokers were found to be at a statistically significantly increased risk for coronary heart disease and stroke. There was a close and statistically significant association between smoking and chronic obstructive lung diseases, respiratory tuberculosis, and other respiratory infections. There was also a close dose-response relationship of the number of cigarettes consumed per day to the risk of respiratory tuberculosis and obstructive lung disease.

[Assessing lead cancerogenic effects affecting printing house workers]. / Otsenka kantserogennosti svintsa u rabotnikov tipografii.

The aim of this study was to determine the level of risk of occupational cancer among compositors exposed to inorganic lead. A total of 216 men and 423 women were included in the cohort and followed up from 1 January 1979 to 31 December 1993. There were 2759 person-years among males and 6050 person-years among females. Among men, employed as compositors, there was a significantly elevated mortality from pancreas cancer. We have found two deaths from kidney cancer occurred exclusively among women-compositors with exposure 20 years or more yielding significantly increased SMR of 10.0.

[Epidemiology, mechanisms of cancerogenesis and prevention of neoplasms]. / Epidemiologiia, mekhanizmy kantserogeneza i profilaktika raka.

Primary prevention is the priority in cancer fighting. Smoking control is the most important measure in primary prevention of cancer. Dietary factor is also essential. Modification of diet with an increase in consumption of fresh fruit and vegetables, low-calory products, intensification of physical activity and lowering of body mass produce a reduction in the incidence of cancer of the stomach, large bowel, breast, corpus uteri, prostate. Prevention of infection including vaccination is the most efficient method for prevention of cancer of the liver, cervix uteri, some leukemias and lymphomas, H. pylori associated stomach cancer. Control of environmental hazards such as intensive ultraviolet radiation, ionizing radiation, air and soil pollution decrease the rate of skin cancer, melanoma, etc. The progress in molecular biology allows to modify carcinogenesis at each stage of cancer. Cancer risk assessment can be based not only on the knowledge of carcinogenicity of environmental factor and its dose but also on the information about individual genetic susceptibility. Information about carcinogen-specific somatic genetic damage (finger prints) and tumor-specific molecular changes in oncogenes and tumor suppressor genes can be used for identification of causative factors and early preclinical molecular diagnosis of cancer.