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Epidemiology of cancer of the nose and paranasal sinuses: current concepts.

Cancer of the nose and paranasal sinuses (SNC) has been attributed to occupational exposure to nickel, chromium, radium, dichlordiethyl sulphide, isopropyl oil, and hydrocarbons. Occupational groups with an increased SNC risk include furniture, boot and show workers, and workers in U.S. countries heavily involved in both petroleum and chemical manufacturing; specific agents have not been identified with certainty. In most of the studies, the risk for developing SNC in the exposed workers was 21 to 100+ times greater than the risk for SNC in those who were not exposed. Undifferentiated and squamous histologies are associated with nickel refining; adenocarcinomas are found in woodworkers, boot and show manufacturers, and textile workers. Most occupations at risk for SNC were also at risk for cancer of other sites, particularly lung and skin cancer. Study of the epidemiology of SNC may identify unrecognized carcinogens and occupational groups at increased cancer risk.

Adenocarcinoma↗

Hepatocellular carcinoma after thorotrast exposure: establishment of a new cell line (Mz-Hep-1).

A human hepatoma cell line, associated with thorotrast exposure, from an hepatitis B marker-negative patient was established as a permanent cell line (Mz-Hep-1) in tissue culture. Histology of the primary tumor, as well as phase contrast, transmission and scanning electron microscopy of the cultured cells showed typical characteristics of liver cells. Mz-Hep-1 cells secreted complement components (C2, C3, C4), carcinoembryonic antigen, lactate dehydrogenase, chymotrypsin, haptoglobin and retinol-binding protein and expressed HLA-, transferrin-, blood group B-related determinants and complement component C5 and carcinoembryonic antigen on their cell surface. Mz-Hep-1 cells represent the first human hepatoma cell line, which is strongly associated with a carcinogen.

Angiography↗

Microsatellite instability in thorotrast-induced human intrahepatic cholangiocarcinoma.

Thorotrast, a colloidal suspension of radioactive (232)ThO(2) that emits alpha particles, was used as a radiographic contrast during World War II. It is known to induce liver cancers, most frequently ICC, decades after injection. Since radiation induces genomic instability, we analyzed MSI in Thorotrast-induced ICC. The frequency of MSI(+) cases was 62.5% in Thorotrast ICC, whereas it was 22.7% in non-Thorotrast ICC. However, frameshift mutations of mononucleotide repeats were not observed in Thorotrast ICC. In addition, the MSI(+) phenotype was not associated with the quantity of Thorotrast deposited or the latency period of ICC induction. Promoter regions of both the hMLH1 and the hMSH2 MMR genes tended to be hypermethylated in the tumor part compared to the adjacent nontumor part in Thorotrast ICC. Methylation of the hMLH1 promoter was associated with the MSI(+) phenotype in Thorotrast ICC. In contrast, methylation status of these promoter regions was not related to MSI in non-Thorotrast ICC cases. These findings suggest that MSI induced by exposure to Thorotrast mainly reflects clonal expansion of cancer cells and is partly due to inactivation of hMLH1 by hypermethylation.

Adaptor Proteins, Signal Transducing↗

Lung carcinoma and malignant mesothelioma in patients exposed to Thorotrast: incidence, histology and p53 status.

In a previous registry-based survey of 999 patients injected with alpha-emitting 232ThO2 (Thorotrast), we identified elevated risks for lung carcinoma and malignant mesothelioma. Since injected Thorotrast is retained lifelong mostly in liver, spleen and lymph nodes, the mesothelial surfaces of these organs are constantly irradiated. Thorotrast-administered patients also perpetually exhale 220Rn, a 232Th-daughter. Study of Thorotrast-exposed patients may, therefore, provide data with regard to carcinogenicity of radon exposure, a current public health concern, as well as the pathogenesis of malignant mesothelioma. The incidence and histologic types of lung carcinoma and malignant mesothelioma within the cohort were examined by review of available histopathologic material and medical records. Further, mutations of the p53 gene were analyzed whenever possible as it has previously been suggested that radon-associated lung carcinomas exhibit specific mutational patterns. The cumulative risk for lung carcinoma reached 11.0% based on 20 confirmed cases. Nine were small cell lung cancer (SCLC), whereas the expected frequency was 18%. The risk for malignant mesothelioma reached 2.5% based on 7 cases. The actuarial risk of malignant mesothelioma for patients given more than 20 ml Thorotrast was 7.8% compared to 1.4% for patients administered smaller amounts. Seven lung carcinomas and 5 malignant mesotheliomas were analyzed for p53 mutations; only 1 (in a lung adenocarcinoma) was detected. A possible association between Thorotrast and SCLC is suggested. In addition, a possible dose-response gradient exists for Thorotrast and malignant mesothelioma.

Adolescent↗