Occupational Carcinogen Exposure Research Articles

SALTRA: A Regional Program for Workers' Health and Sustainable Development in Central America

In 2003, the university-based Program on Work and Health in Central America, SALTRA, was launched to build national and regional capacities in occupational safety and health with the goal of preventing and reducing poverty in Central America. SALTRA has implemented 20 projects including action projects in priority sectors (e.g., construction, sugarcane, hospitals, migrant coffee workers); strengthening of surveillance (occupational health profiles, carcinogenic exposures, fatal injuries and pesticides); a participatory model for training and risk monitoring by workers; building occupational health capacity for professionals, employers, and workers, with collaborating networks between the countries; strengthening of universities in work, environment, and health; studies of serious occupational and environmental situations; communication channels; and continued efforts to raise political awareness. SALTRA has placed issues of workers' health on political, business, and academic agendas throughout the region and has laid the foundations for achieving substantial future improvements in health conditions of all workers in the region. External evaluators envisioned SALTRA as an innovative development model.

Update of cancer and non‐cancer mortality in the Missouri poultry cohort

workers in poultry slaughtering and processing plants have one of the highest human exposures to transmissible agents that cause cancer and other diseases in chickens and turkeys, and also have other occupational carcinogenic exposures. The general population is also exposed to these transmissible agents. we investigated mortality in workers who belong to a poultry union in Missouri, and estimated standardized mortality ratios. significantly increased mortality was observed for some leukemias, benign neoplasms, thyroid diseases, bacterial infections, and schizophrenic disorders. The risk of breast cancer and several non-cancer conditions was significantly depressed. the findings add to the growing evidence suggesting that workers occupationally exposed to transmissible agents and carcinogens in the poultry industry, are at increased risk of dying from certain chronic diseases, including cancer.

Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund

Background The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. Objective To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. Methods Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. Results Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. Conclusion This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures.

Estimates of work-related cancers in workers exposed to carcinogens

To evaluate the proportion of work-related cancers. A descriptive study of incident cases of cancer during 3 years in a French county. All people with cancer having a current or past working history were included in the studied population which was recruited from local hospitals. A working history was obtained from each subject by interview. The different organ cancers were linked using well-defined criteria, to specific occupational carcinogenic exposures. The results obtained were compared to international data on work-related cancer incidences. A total of 2009 cases were included and 3.18% (64) met the criteria for work-related cancer as defined. Asbestos and polycyclic hydrocarbons were the main occupational carcinogens identified. Construction and fabricated metal products sectors were linked to almost two-thirds of work-related cancers. The percentage of the studied population with attributable risk for occupational cancer was relatively close to international data (mean 4%) and organ cancer distribution percentages did not vary significantly from international published validated data. Work-related cancers tend to be concentrated in relatively small groups of people among whom the risk of developing the disease may be quite large. The detection of occupational hazards should therefore have a higher priority in any programme of cancer prevention. Well-defined criteria to identify specifically cancers with an occupational origin should be specified by the scientific international community.

Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: effects on levels of sister chromatid exchanges and chromosomal aberrations

Elevated levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes, widely used as a cytogenetic biomarker of genotoxic effects, have been linked to cancer predisposition. However, tobacco smoking, occupational carcinogen exposure, or time since CA analysis do not appear to explain the cancer predictivity of CAs. Alternatively, the observed CA-cancer association could reflect unidentified exposures or individual susceptibility. We assessed the effects of genetic polymorphisms of DNA repair proteins and xenobiotic-metabolizing enzymes (XMEs) on the levels of CAs and sister chromatid exchanges (SCEs) in peripheral lymphocytes of 145 (CAs) and 60 (SCEs) healthy Caucasians. Genotypes of DNA repair genes X-ray repair cross-complementation group 1 ( XRCC1 codons 194, 280, 399) and 3 ( XRCC3 codon 124), and XME genes glutathione- S-transferase ( GST) M1 and T1 and N-acetyl transferase 2 ( NAT2) were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP)-based methods. After Poisson regression adjustment for age, sex, smoking, country, and genotypes, a higher frequency of chromosome-type breaks was observed for NAT2 slow acetylators (in nonsmokers) and GSTT1 null subjects (in smokers). Individuals carrying variant alleles for XRCC1 codons 280 and 194 showed a decreased level of chromosome-type breaks. The effect of GSTM1 null and XRCC1 codon 399 genotypes on the frequency of CAs was modified by smoking. In linear regression models adjusting for age, sex, smoking, and genotypes, none of the polymorphisms significantly affected SCE frequency, although GSTT1 null subjects had a slightly elevated SCE level. Our results are in line with earlier findings on the influence of NAT2, GSTT1, and GSTM1 polymorphisms on the level of lymphocyte chromosome damage and suggest that also XRCC1 polymorphism affects CA frequencies, thus apparently influencing DNA repair phenotype. It remains to be examined whether these or other genetic polymorphisms could explain the observed cancer risk predictivity of high CA frequency.

Environmental exposure to carcinogens causing lung cancer: epidemiological evidence from the medical literature.

In 2000 there were 1.1 million lung or bronchial cancer deaths worldwide, with relatively limited evidence of causation other than for smoking. We aimed to search and appraise the literature regarding evidence for a causal relationship between air pollution and lung cancer according to the 10 Bradford Hill criteria for causality. A MEDLINE search was performed using the following key words: 'lung neoplasm', 'epidemiology', 'human', 'air pollution'and 'not molec*'. The criteria for inclusion was: cited original research that described the study population, measured environmental factors, was of case control or cohort design, and was undertaken after 1982. Fourteen papers (10 case control, four cohort studies) fulfilled the search criteria, with a sample size ranging from 101 cases and 89 controls, to a cohort of 552 cases and 138 controls. Of the 14 papers that fulfilled the search criteria the number of papers addressing each of the Bradford Hill criteria were as follows: Strength of association: eight studies demonstrated significant positive associations between environmental exposure and lung cancer with a relative risk range of 1.14-5.2. One study found a negative association with relative risk 0.28. Consistency: eight of 14 studies found significant positive associations and one of 14 a significant negative association. Specificity: tobacco smoking and occupational exposure were addressed in all studies (often crudely with misclassification). Temporality: exposure prior to diagnosis was demonstrated in nine studies. Dose-response relationship: evident in three studies. Coherence, analogy: not addressed in any study. Evidence for causality is modest, with intermediate consistency of findings, limited dose-response evidence and crude adjustment for important potential confounders. Large studies with comprehensive risk factor quantification are required to clarify the potentially small effect of air pollution given the relatively large effects of tobacco smoking and occupational carcinogen exposure.

Occupational and nonoccupational factors associated with high grade bronchial pre-invasive lesions.

Besides tobacco exposure, factors associated with the development of pre-invasive bronchial lesions are not known. Autofluorescence bronchoscopy was used to assess the prevalence of severe dysplasia and carcinoma in situ (SD/CIS) of the proximal bronchial tree in relation to occupational or nonoccupational carcinogen exposure. Among the 241 individuals in this study, the overall prevalence of at least one SD/CIS was 9% (21 subjects). Multivariable analysis revealed significant and independent associations between presence of SD/CIS and: 1) active smoking, relative to former smokers; 2) presence of synchronous invasive lung cancer; 3) duration of asbestos exposure and; 4) exposure to other occupational carcinogens. The independent associations of synchronous lung cancer with severe dysplasia and carcinoma, after adjusting for both occupational and nonoccupational carcinogen exposures, suggest other mechanisms than a field cancerisation may be involved in the carcinogenesis of these pre-invasive lesions. Moreover, active smokers, patients with recently resected invasive lung cancer and workers occupationally exposed to bronchial carcinogens may represent a population of choice for early cancer endoscopic detection programmes in view of their high severe dysplasia and carcinoma prevalence.

FOLLOW-UP GENOTOXICOLOGICAL MONITORING OF NURSES HANDLING ANTINEOPLASTIC DRUGS

Most of the antineoplastic drugs used in the treatment of tumors are carcinogenic to humans. Hospital nurses are often subject to possible occupational carcinogen exposure. Exposure may occur during handling and administration of infusion solutions containing cytostatics. A genotoxicological monitoring system to detect genotoxic changes was developed in our laboratory, helping to improve working conditions and subserving primary prevention. Multiple-endpoint follow-up genotoxicological monitoring was performed in peripheral blood lymphocytes (PBLs) among 4 groups of 95 nurses (152 investigations) occupationally exposed to cytostatics. The results were compared to those of historical and industrial controls. The genotoxicological endpoints were the determination of the frequency of sister chromatid exchanges (SCEs) and the cells with high-frequency SCEs (HFC), the frequency of structural and numerical chromosome aberrations, and the measurement of ultraviolet-light-induced unscheduled DNA-repair synthesis (UDS). In Hospital 1, where nurses worked without a safety cabinet, the percentage of cells with chromosome aberrations (AC) was significantly higher than that of the controls. In Hospital 2, where nurses used inadequate safety cabinets (with horizontal airflow), significantly elevated levels of AC, SCE, HFC, and UDS were detected. During follow-up, in Hospital 2 at the time of the second investigation AC was still significantly higher, although safety conditions had been improved. The results indicate the presence of genotoxic damage in hospital nurses working with no or inadequate safety equipment. In Hospitals 3 and 4 where nurses using biological safety cabinets, the results were lower than those in the previous two groups. In Hospital 3 in the first year of the study AC was as at the level of industrial controls. During follow-up in the course of the repeated investigations a fluctuation in AC above the control level and an increase in HFC in yr 4 and 6 of the study were observed. In this group, the fluctuation in AC and HFC during the study points to the possibility of genotoxic exposure with cytostatics despite of the use of suitable safety cabinets, drawing attention to other possible routes of exposure. In Hospital 4, both AC and HFC were elevated. These data corroborate the need to maintain safety measures to avoid exposure, and the necessity of intervention in the case of exposure when using and handling hazardous carcinogenic agents. The results also indicate a certain expression time for genotoxic changes, which can lead to late somatic mutations as well as to a possible higher risk of cancer.

SMOKING AND THE MOLECULAR EPIDEMIOLOGY OF LUNG CANCER

Lung carcinogenesis in humans requires exposure to environmental agents, including the inhalation of tobacco smoke, radioactive compounds, asbestos, heavy metals, and petrochemicals. Tobacco smoking is the risk factor with the highest attributable lung cancer risk worldwide. This article discusses occupational carcinogen exposure and exposure from tobacco use, and the lung-cancer risk associated with these types of exposure.

Recent developments in the multistage modeling of cohort data for carcinogenic risk assessment.

The modeling of cohort data based on the Armitage-Doll multistage model of the carcinogenic process has gained popular acceptance as a methodology for quantitative risk assessment for estimating the dose-related relationships between different occupational and environmental carcinogenic exposures and cancer mortality. The multistage model can be used for extrapolation to low doses relevant for setting environmental standards and also provides information regarding whether more than one stage is dose-related, which assists in determining whether different carcinogens affect different stages of the cancer process. This paper summarizes recent developments in the multistage modeling of cohort data and emphasizes practical issues such as handling data arising from large epidemiologic follow-up studies, the time-dependent nature of exposures and statistical issues such as multicollinearity in time-related variables, robustness of parameter estimates, validating of the fitted models, and routine inferential procedures. Problems related to uncertainties of risk estimates are discussed also. Computer programs for fitting multistage models with one or two dose-related stages to cohort data incorporating time-dependent exposure patterns; constructing confidence regions for model parameters; and predicting lifetime risks of dying from cancer adjusting for competing causes of death are detailed. Illustrations are provided using lung cancer mortality in a cohort of nonwhite male coke oven workers exposed to coal tar pitch volatiles.

The Epidemiologic Necropsy

To the Editor.— McFarlane and colleagues 1 have recently published an article based on 159 necropsy-proved cases of lung cancer during a 12-year period at one medical center. They suggest that there may be a large and undiagnosed reservoir of lung cancer cases in the population, that the relationship between smoking and lung cancer is overstated, and that the observed increase in the rate of lung cancer in women is due to occupational carcinogen exposure. It is hardly surprising that patients pass through a stage during which their lung cancer is either asymptomatic or symptomatic but unsuspected by their physician. Nor is it surprising that some patients with lung cancer will die of other diseases. As indicated in the article, most of these deaths are due to diseases that are related to tobacco smoking (ie, myocardial infarction, pneumonia, and stroke). Of the 2996 necropsies performed, lung cancer was found as