Our results lend support to the hypothesis that occupational PAH exposure causes fatal IHD and demonstrate a consistent exposure-response relation for this association.

Objectives-Consolidation of epidemiological data on pancreatic cancer and worksite exposures. Methods-Publications during 1969-98 were surveyed. Studies without verified exposures were excluded. Meta-analyses were conducted on data from 92 studies covering 161 populations, with results for 23 agents or groups of agents. With a standard format, five epidemiologists extracted risk estimates and variables of the structure and quality of each study. The extracted data were centrally checked. Random meta-models were applied. Results-Based on 20 populations, exposure to chlorinated hydrocarbon (CHC) solvents and related compounds was associated with a meta-risk ratio (MRR) of 1.4 (95% confidence interval (95% CI) 1.0 to 1.8). Nickel and nickel compounds were considered in four populations (1.9; 1.2 to 3.2). Excesses were found also for chromium and chromium compounds (1.4; 0.9 to 2.3), polycyclic aromatic hydrocarbons (PAHs) (1.5; 0.9 to 2.5), organochlorine insecticides (1.5; 0.6 to 3.7), silica dust (1.4; 0.9 to 2.0), and aliphatic and alicyclic hydrocarbon solvents (1.3; 0.8 to 2.8). Evidence on pancreatic carcinogenicity was weak or non-positive for the following agents: acrylonitrile (1.1; 0.0 to 6.2); arsenic (1.0; 0.6 to 1.5); asbestos (1.1; 0.9 to 1.5); diesel engine exhaust (1.0; 0.9 to 1.3); electromagnetic fields (1.1; 0.8 to 1.4); formaldehyde (0.8; 0.5 to 1.0); flour dust (1.1; 0.3 to 3.2); cadmium and cadmium compounds (0.7; 0.4 to 1.4); gasoline (1.0; 0.8 to 1.2); herbicides (1.0; 0.8 to 1.3); iron and iron compounds (1.3; 0.7 to 2.5); lead and lead compounds (1.1; 0.8 to 1.5); man-made vitreous fibres (1.0; 0.6 to 1.6); oil mist (0.9; 0.8 to 1.0); and wood dust (1.1; 0.9 to 2.5). The occupational aetiological fraction of pancreatic cancer was estimated at 12%. In a subpopulation exposed to CHC solvents and related compounds, it was 29%; to chromium and chromium compounds, 23%; to nickel and nickel compounds, 47%; to insecticides, 33%; and to PAHs, 33%. Conclusion-Occupationalexposures may increase risk of pancreatic cancer. High quality studies are called for on interactions between occupational, environmental, and lifestyle factors as well as interactions between genes and the environment. (Occup Environ Med 2000;57:316-324) Keywords: pancreatic cancer; occupational exposure; meta-analysis Some 180 000 pancreatic cancers are registered annually in the world. It is highly and rapidly fatal and represents the fifth leading cause of deaths from cancer in industrialised countries and is 50%-100% more common in men than in women. It is not consistently associated with socioeconomic status within national populations, although there is a tendency toward higher age adjusted risk in richer than poorer countries.

No abstract

Twenty epidemiologic studies have described cancer risk in asphalt workers and roofers in various countries. A current concern for these workers is the potential carcinogenicity posed by inhalation of bitumen fumes or dermal exposure to bitumens. Bitumens are chemically different from many carcinogenic coal-tar based materials. Both have been employed in road paving and waterproofing. We examined and combined the results of the epidemiologic studies conducted on asphalt workers and roofers. We examined the cancer risk separately in three broad job categories: 1) roofers (exposed to bitumen fumes and previously often to coal-tar fumes); 2) highway maintenance workers (HMWs) and road pavers (exposed to bitumen fumes as well as possibly coal-tar fumes previously); and 3) miscellaneous and unspecified bitumen/asphalt workers. In roofers, an increased risk was suggested for cancers of the lung (aggregated relative risk 1.8, 95% confidence interval 1.5-2.1), stomach (1.7, 1.1-2.5), nonmelanoma skin (4.0, 0.8-12), and leukemia (1.7, 0.9-2.9). Some of the excesses may be attributable to polycyclic aromatic hydrocarbons (PAH) from coal-tar products. The aggregated relative risks in road pavers and HMWs were consistently lower than in roofers for cancers of the lung (0.9, 0.8-1.0), stomach (1.1, 0.8-1.5), bladder (1.2, 0.7-1.8), skin (2.2, 1.2-3.7), and leukemias (1.3, 0.9-1.8). Their risk of skin cancer was significantly increased, based on one study. Miscellaneous and unspecified workers had a significant excess (1.5, 1.2-1.8) of lung cancer. The data were poorly focused to address the carcinogenicity of bitumen fumes, as contrasted with tar-derived exposures. For the prospect of shedding more light on the bitumen-cancer controversy, the feasibility of a powerful multicenter cohort is currently being studied by the International Agency for Research on Cancer (IARC).

Large worker populations in the Third World are exposed to increasing amounts of pesticides, including pesticides severely restricted and banned in industrialized countries. Studies on knowledge, attitudes, and practices indicate that unsafe use of pesticides is the rule in Third World countries. Surveys of acute poisonings show high rates in these countries, despite underregistration. The scarce studies on chronic health outcomes demonstrate neurotoxic, reproductive, and dermatologic effects. Exposure assessment consists mainly of cholinesterase testing, and few studies have quantified dermal and respiratory exposure. The few intervention studies demonstrate the need for evaluation of the impact of preventive measures and policies. There is no evidence that widespread "safe-use" programs have greatly affected exposure and morbidity. It was concluded that research should focus on simple methods for surveillance of exposure and on surveillance of acute illness and its causes in order to develop and evaluate rapid local interventions. Studies on chronic effects should be carried out in selected countries, aiming at long-term and broader interventions. Policies that promote the use of pesticides should be critically evaluated. North-South and South-South research collaborations must be encouraged to address this global health problem.

PARTANEN T, HEIKKILA P, HERNBERG S, KAUPPINEN T, MONETA G, OJAJARVI A. Renal cell cancer and occupational exposure to chemical agents. Scand J Work En viron Health 1991; 17:231-9. A case-referent study of occupational risk indicators of renal cell adenocarcinoma was conducted. Each incident case in Finland in 1977-1978 was matched with two population referents. Lifelongjob histories were collected and translated into indicators of industry, occupation, and occupational exposures. The analyses of 338 sets of cases and referents revealed elevated risks for a history of employment in whitecollar occupations; the printing industry; the chemical industry; the manufacturing of metal products; mail, telephone, and telegraph services; and iron and metalware work. A decreased risk was observed for male farmers. An elevated risk and an exposure-response relationship were found for gasoline exposure. The excess risk was highest at a latency period of approximately 30 years. The findings support the hypothesisthat exposureto some constituent(s) of gasolineincreases the incidenceof renal adenocarcinoma in humans. Suggestions of elevated risks appeared for exposures to inorganic lead, cadmium, and nonchlorinated solvents.

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 (> or = 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.

Until the introduction of self-service around 1970, service station workers in the Nordic countries were exposed to gasoline vapors. Based on measurements reported in the literature, the 8-hour time-weighted average benzene exposure was estimated to be in the range of 0.5-1 mg/m3. We studied the cancer incidence in a cohort of 19,000 service station workers from Denmark, Norway, Sweden, and Finland. They were identified from the 1970 censuses and followed through 20 years, where 1,300 incident cancers were observed. National incidence rates were used for comparison. The incidence was not increased for leukemia (observed = 28, standardized incidence ratio (SIR) = 0.9, 95% confidence interval (CI) 0.6-1.3) not for acute myeloid leukemia (observed = 13, SIR = 1.3, 95% CI 0.7-2.1). The incidence was slightly elevated for kidney cancer observed = 57, SIR = 1.3, 95% CI 1.0-1.7) and for pharyngeal, laryngeal, and lung cancer. A 3.5-fold risk of nasal cancer was found (observed = 12, SIR = 3.5, 95% CI 1.8-6.1). This cohort exposed to gasoline vapors with benzene levels estimated to be 0.5-1 mg/m3 showed no excess risk of leukemia or acute myeloid leukemia, a 30% elevated risk of kidney cancer, and a previously unnoticed risk of nasal cancer.