Proportion of lung cancers in males, due to occupation, in different areas of the USA

Occupational data from 5 case-control studies in the United States involving 2,973 male cases and 3,210 controls were analyzed to estimate the percentage of lung cancer attributable to well-known and suspected lung carcinogens. The studies were conducted in areas heterogeneous in terms of industrial activities. The percentage of lung cancers attributable to occupations entailing potential exposure to well-recognized carcinogens ranged, by study area, from 3 to 17%. The further inclusion of occupational groups with suspect carcinogenic exposures changed these estimates very little. Exclusion of data derived from next-of-kin interviews influenced the estimates of attributable risks, but not in a systematic fashion. The estimates also varied according to ethnic group, smoking status and birth cohort, with higher values in non-whites, non-smokers and among members of more recent birth cohorts. Possible errors in exposure classification, which may make these estimates conservative, are discussed.     

Incidence of digestive cancers and occupational exposure to asbestos.

While the role of exposure to asbestos in the development of several cancers such as mesotheliomas and bronchopulmonary cancers is now well established, the possible relationship between digestive cancers, other than peritoneal mesotheliomas, and occupational exposure to asbestos is still controversial. The great majority of the studies are based on mortality data. The aim of the study was to analyse the relationship between digestive cancer incidence and occupational exposure to asbestos in a population of subjects for whom precise occupational exposure data and precise incidence data were available. The population consisted of salaried and retired workers from a company using asbestos to manufacture fireproof textiles and friction materials. There were 1454 men (79.9%) and 366 women (20.1%). A cumulative exposure index and a mean exposure concentration in fibres/ml for each subject were calculated with the aid of an in-house job-exposure matrix. The number of cases of digestive cancer observed was compared with the expected and Standardized Incidence Ratio (SIR) was estimated. Precise occupational exposure data allowed us to study the dose-response relationship between asbestos exposure and risk of digestive cancer using Cox model. Fifty-six digestive cancers occurred in the study population over the 18-year follow-up period for 48.4 expected (SIR = 1.16 [0.87-1.50]). Comparing with incidence in the county, SIR was not significant for any of the digestive localization, but for peritoneum. However, even after taking into account the potential confounders via the Cox model, there was a significant dose-response relationship between the occurrence of digestive cancers and the mean exposure concentration, even after exclusion of peritoneum cancers. Our study provides initial evidence suggesting a relationship between occupational exposure to asbestos and the risk of digestive cancer: first, it is a study of incidence although the risk evidenced is not significant; secondly, a dose-effect relationship is demonstrated in the whole population. However, these preliminary results require confirmation by more powerful studies focusing on larger series.     

Estimates of the proportion of lung cancer attributable to occupational exposure

The proportion of lung cancer due to occupational exposure hasbeen estimated by computing the attributable risk in the population(ARp) from various case-control studies. Different criteriahave been used in including occupational exposures from publishedstudies: (i) exposure to lung carcinogens according to a job-exposurematrix approach; (ii) occupations in which an increased riskof lung cancer has been established; (iii) occupations in whichan increased risk of lung cancer has been suggested; and (iv)occupations associated with a statistically significant increaseof lung cancer. Only studies in which the confounding effectof smoking was controlled for have been included. We found awide variability of ARp estimates, mainly due to the differentgeographical locations of the studies, while they seem to beonly moderately affected by the different criteria of inclusionof the relevant occupational exposures. Studies using job-exposurematrices gave ARps ranging from 0.6% to 35%. When a list of recognized carcinogenic exposures was used for the selectionof the relevant occupations, the estimates varied between 2.4%and 40%. From the studies reviewed it also appears that tobaccosmoking has a very limited confounding effect. Various limitationsof the exercise are discussed.     

Residential and occupational exposure to 50 Hz magnetic fields and hematological cancers in Norway

Objective: The aim of this nested case–control study was to test the hypothesis that exposure to electromagnetic fields from high-voltage power lines increases the incidence of hematological cancers in adults. Data from an occupational exposure matrix was also used. Methods: The study population comprised subjects aged 16 and above who had lived in a residence situated in a broad corridor around a high-voltage power line in 1980, or one of the years from 1986 to 1996. The cases were incident cases diagnosed 1980–1996. Two controls were matched to each case by year of birth, sex, municipality and first year entering the cohort. Time-weighted average exposure to residential magnetic fields generated by the power lines was calculated for the exposure follow-up from January 1, 1967 until diagnosis using cut-off points at 0.05 and 0.20 T. In addition, job titles and industrial branch was classified as categories of hours per week in a magnetic field above background (0.1 T). Subjects exposures were cumulated over occupationally active years for the exposure follow-up January 1, 1955 until diagnosis. Results: When residential magnetic fields are evaluated, the two upper residential time weighted average magnetic field categories showed non-significant elevated odds ratios (ORs) for all leukemia combined (OR: 1.3, 95% confidence interval (CI) 0.7–2.5 and OR: 1.5, 95% CI: 0.8–3.0). The increased risk was confined to chronic lymphocytic leukemia, acute lymphocytic and acute myeloid leukemia. Lymphoma showed a non-significant lower OR in the upper exposure category. Multiple myeloma showed non-significant elevated ORs. Occupational exposure showed no significant association to exposure for any site. Conclusions: Some elevated ORs were observed in the present study, but the results are based on small numbers and no firm conclusions can be drawn.     

News in occupational cancers

Despite the knowledge of the link between many sites of cancer occurence and previous occupational exposure, occupational cancers are generally underestimated. These cancers can be prevented through specific plans. In France, the number of cases requesting and receiving compensation for occupational cancer is increasing. The frequency of occupational exposure to carcinogens was recently evaluated. Legislation was reinforced in order to obtain a better control of exposure to carcinogens in the workplace. Lung cancer is the most frequent of occupational cancers. Epidemiological studies contribute to a better knowledge of etiologies and occupations responsible for the outcome of these cancers and allow quantification of the risk of cancer linked to different situations of exposure. Beside classical epidemiological studies, molecular epidemiology aims at identifying molecular targets of occupational agents. This approach may allow a better knowledge of the part played by occupational agents in these multifactorial diseases.     

Cancer risks due to occupational exposure to formaldehyde: results of a multi-site case-control study in Montreal

A case-control study was undertaken in Montreal to investigate the possible associations between occupational exposures and cancers of the following sites: oesophagus, stomach, colo-rectum, liver, pancreas, lung, prostate, bladder, kidney, melanoma and lymphoid tissue. In total, 3,726 cancer patients and 533 population controls were interviewed to obtain detailed lifetime job histories and information on potential confounders. Each job history was translated into a history of occupational exposures. Because of current concerns about formaldehyde carcinogenicity, we carried out a special analysis of the association between exposure to formaldehyde and each type of cancer covered by this study. Separate statistical analyses were carried out for each type of cancer using population controls as well as a control series drawn from among the other cancer sites in the study. Although nearly a quarter of all subjects had undergone occupational exposure to formaldehyde, the levels of exposure were in general quite low. There was no persuasive evidence of an increased risk of any type of cancer among men exposed to these levels of formaldehyde. However, the possibility of a small increase in risk could not be ruled out.     

Biological monitoring of occupational exposure to nickel

Biological monitoring and hygienic monitoring complement each other in assessing occupational exposure to nickel. Biological monitoring is mainly directed to following the exposure of individual workers. In order to estimate exposure from data on biological monitoring, the exposing agent, i.e., the chemical species of nickel involved must be known. Comparisons between exposures are most reliable when made under similar exposure conditions. In particular, when urine is monitored, contamination of the sample from the dust in the air, workers' clothes, and hands, is a major problem. The sampling time must be standardized. At present, no clear-cut preference can be given to plasma rather than urine or vice versa. With the exception of nickel carbonyl poisoning, no health risk estimation can be performed based on the results of biological monitoring. Cytogenetic methods do not seem appropriate for assessing risk or exposure. The increase in chromosome gaps reported in one study seems to indicate the need for further research.     

Smoking status,occupational asbestos exposure and bronchial location of lung cancer

The objective of this study was to determine the factors associated with central airway versus peripheral bronchial location of lung cancer. All patients diagnosed with lung cancer from 1997 through 2000 in the Respiratory Disease Department of Rouen University Hospital were prospectively interviewed about their smoking and occupational history using a standardized questionnaire. All patients underwent white-light bronchial endoscopy using a 4.5 mm flexible endoscope. Tumors were classified as central when they were accessible and visible using this technique. Out of 217 cases of lung cancer included in this study, 155 (71%) were central. Histological type of lung cancer was strongly associated with bronchial location as central location was observed in 48, 82 and 92% of Adenocarcinoma (AC), Squamous Cell (SqC), and Small Cell Carcinoma (SCC), respectively (P<0.0001). Among non asbestos-exposed patients, location varied little with smoking status, with central location frequency ranging from 74 to 80%. In contrast, lung cancer was recorded central in 41% of long-term (> or =10 years) ex-smokers, 67% of short-term (<10 years) ex-smokers and 75% of current smokers (P=0.04) among patients exposed to asbestos, suggesting an interaction between duration of smoking cessation and occupational asbestos exposure with respect to lung cancer location. These findings were confirmed after adjustment for sex, age and histologic type in multivariate analysis. These results suggest that individually-tailored multimodality screening strategies relying on various combinations of low-dose CT scan, sputum analysis and fluorescence endoscopy according to each patient's profile may be more effective than standard strategies based on a single approach for all patients.     

Cancer in relation to occupational exposure to perchloroethylene

Exposure to perchloroethylene (PCE) occurs in a number of occupational settings in which organic solvents are used, and, in particular, is widely prevalent in the dry-cleaning industry. This review summarizes the results of studies of the occurrence of the individual types of cancer in dry cleaners. Two of those cancers of greatest a priori concern (because of results in PCE-exposed experimental animals)-liver cancer and leukemia-have not occurred with increased frequency among persons employed in the dry-cleaning industry. Rates were elevated by about a factor of two for esophageal and bladder cancers, but not increased clearly for any other site. The excess mortality from esophageal cancer was well beyond the limits of chance, based on a total of 23 deaths that occurred in the two principal cohort-studies of dry cleaners. There was some indication of a particularly high risk associated with prolonged employment and a long interval since first employment. However, the possible confounding effect of the combination of cigarette smoking and heavy alcohol consumption, a very strong risk factor for the development of esophageal cancer, could be taken into account only partially in these studies. With regard to bladder cancer, the limited data available suggest that the observed increased risk could be due to exposure to other solvents than PCE used in dry cleaning. The potential influence of occupational exposure to PCE on the occurrence of esophageal and bladder cancer needs continued examination in further follow-up of existing cohorts of dry cleaners, the assembly of additional cohorts, and in large case-control studies that ascertain occupational exposures in some detail.Dr Weiss is with the University of Washington and the Fred Hutchinson Cancer Research Center, Seattle, WA. Address correspondence to Dr Weiss, University of Washington, Department of Epidemiology, SC36 Seattle, WA 98195, USA. This work was supported by the Halogenated Solvents Industry Alliance.     

A quantitative assessment of lung cancer risk and occupational cadmium exposure.

We have performed a quantitative assessment of the risk of lung cancer from exposure to cadmium based on a retrospective cohort mortality study of cadmium-exposed workers. The findings were analysed using a life-table analysis to estimate standardized mortality ratios (SMRs), and various functional forms of Poisson and Cox proportionate hazards models to examine dose-response relationships. An excess mortality from lung cancer was observed for the entire cohort (SMR = 149,95% CI = 95-222). Lung cancer mortality was significantly elevated among non-hispanic workers, among those in the highest cadmium-exposure group, and among workers with 20 or more years since first exposure. A statistically significant dose-response relationship was evident in nearly all of the regression analyses. Based on our analyses, the lifetime excess lung cancer risk at the current OSHA standard for cadmium fumes of 100 micrograms/m3 is approximately 50-111 lung cancer deaths per 1000 workers exposed to cadmium for 45 years.     

K-ras mutations in human adenocarcinoma of the lung: Association with smoking and occupational exposure to asbestos

We investigated point mutational activation of the ras genes (K-ras codons 12, 13 and 61; N-ras codons 12, 13 and 61; H-ras codons 12 and 61) in primary, resected lung cancer by dot blotting and oligonucleotide hybridization. K-ras mutations were found in 14 (29%) of the 48 lung tumour specimens examined, but no N-ras or H-ras mutations were found. The highest frequency of K-ras mutation was observed in adenocarcinoma: 12 of the 21 samples studied (57%) had a mutation, which is one of the highest frequencies reported for lung adenocarcinoma. The commonest type of mutation in these lung tumour samples consisted of transversions: we observed 11, of which 8 (57% of all mutations) were G to T transversions. Most of the 48 patients studied had a history of heavy smoking, either with or without evidence of occupational exposure to asbestos. Statistical analysis revealed-in addition to the highly significant association between the adenocarcinoma type of lung cancer and K-ras mutation-a clear association of K-ras mutations with heavy life-time smoking (≥50 pack-years of cigarette smoking; odds ratio (OR) 4.9, 90% CI 1.2 - 19.5, multivariate analysis). In addition, occupational asbestos exposure showed an elevated, but non-significant, OR of 2.2 (90% CI 0.6 - 8.7) with the presence of K-ras mutation. We conclude that the occurrence of K-ras mutations in adenocarcinoma of the lung is frequent, and that such mutations are associated with heavy life-time exposure to tobacco smoke, possibly in combination with occupational exposure to asbestos fibres.     

N-mononitrosopiperazine in urine after occupational exposure to piperazine

We have shown previously that intake of the drug piperazine can result in the endogenous formation of N-mononitrosopiperazine (NPZ; Bellander et al., 1985). The present investigation deals with the possibility of endogenous formation of NPZ due to occupational exposure to piperazine in a chemical plant.     

Stomach cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies

Background:

A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer.

Methods:

We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression.

Results:

We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03–1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000.

Conclusions:

Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer.     

Kidney cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies

Objective: To study the risk of kidney cancer following asbestos exposure.Methods: We carried out a meta-analysis of the results of cohort studies of workers predominantly exposed to asbestos. We contacted the authors of 70 cohort studies; published results were available from the reports of 10 cohorts; we obtained the relevant information for an additional 27 cohorts.Results: The studies included in the analysis comprised a total of 169 kidney cancer deaths and 69 incident cases. The overall pooled standardized mortality ratio (SMR) of kidney cancer was 1.1, with a 95% confidence interval (95% CI) of 0.9–1.3. The pooled SMR was higher for workers with undefined asbestos exposure (SMR 1.2, 95% CI 0.9–1.6) than for workers with either predominant chrysotile (SMR 0.9, 95% CI 0.7–1.3) or some amphibole (SMR 0.96, 95% CI 0.6–1.5) exposure. Studies with published results had higher SMRs than studies for which information was obtained from the authors. Studies with high asbestos exposure and an elevated SMR of lung cancer tended to show an increased risk of kidney cancer.Conclusions: It is unlikely that asbestos exposure is responsible for an important increase in kidney cancer risk; however, high asbestos exposure might entail a small increase in risk.     

Evaluation of double cancers in relation to previous asbestos exposure

Ten cases of double cancers (a lung cancer and a stomach cancer) were evaluated in relation to previous asbestos exposure. Ten cases involved male more than 69 years old. Five cases had developed their two cancers simultaneously and other 5 cases had developed their lung cancer after stomach cancer surgery. The lung cancer was their main disease. Four cases had early stage stomach cancers and 5 cases with a stomach cancer had no relapse after surgery. Eight cases had occupational histories of asbestos exposure. Significantly high numbers of asbestos bodies were detected in the autopsied lung in almost all cases. According to the X-ray analysis, almost all asbestos fibers detected in the lung were chrysotile. Additionally, the Brinkman Index (B.I.) of these 10 cases ranged between 700 and 2,000. The combination of asbestos exposure and smoking is thought to be an important factor in the development of such double cancers.     

Bladder cancer and occupational exposure to polycyclic aromatic hydrocarbons

The association between occupational exposure to polycyclic aromatic hydrocarbons (PAH) and bladder cancer development was investigated in a population-based case-control study carried out in the Bormida valley, Italy. One hundred and twenty-one male cases and 342 male controls, matched age, were collected from local hospitals. Occupational exposure to PAH and aromatic amines (AA) was evaluated by means of a job exposure matrix, constructed specifically for this study. Subjects considered as sharing a "definite exposure to PAH" showed an increased risk even after adjustment for cigarette smoking and exposure to AA (OR = 2.14, 95% CL 0.82-5.60). No elevation in risk was found for the category "possible exposure to PAH" (OR = 1.05, 95% CL 0.45-2.44). The findings of this study are consistent with previous studies indicating PAH as a risk factor for bladder cancer. A possible residual confounding effect due to AA impurities is discussed.     

Cancer risk and occupational exposure to aflatoxins in Denmark

A study of cancer risk among male employees at 241 livestock feed processing companies in Denmark was conducted on the basis of a data linkage system for detailed investigation of occupational cancer providing employment histories back until 1964, established at the Danish Cancer Registry. Crops imported for feed production have often been contaminated with highly variable concentrations of aflatoxins; an estimated average concentration of at least 140 micrograms aflatoxin B1 kg-1 prepared mixed cattle feed prevailed in the past, yielding a daily intake for workers via the respiratory route of approximately 170 ng. Risk was established on the basis of cancer cases among male workers, whose employment in one of the companies was the job they had held for the longest time since 1964. Elevated risks for liver cancer and for cancers of the biliary tract were observed, which increased by two- to three-fold significance after a 10-year latency. Exposure to aflatoxins in the imported crops was judged to be the most probable explanation for these findings, although the influence of lifestyle factors, e.g. alcohol consumption on the results cannot be fully disregarded. Increased risks for salivary gland tumours and multiple myeloma were also detected. However, due to multiple comparisons carried out in this study these new associations must await further confirmation. A decreased risk for lung cancer was observed; despite possible negative confounding due to the smoking habits of the employees, the lung does not seem to be a target organ for the carcinogenic effect of inhaled aflatoxins in humans.