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Epidemiologic study of cancer mortality among Israeli asphalt workers.

BACKGROUND: We describe the results of a cancer mortality study among asphalt workers in Israel. METHODS: Personal identifiers and employment histories of 2,176 workers were extracted from company records. RESULTS: Mortality from all malignant neoplasms was significantly reduced in the whole cohort (SMR 0.68, 95% confidence interval (CI) 0.56-0.83). SMR for lung cancer was elevated in workers exposed to bitumen (SMR 1.05, 95% CI 0.62-1.66). No significant elevation or reduction in mortality was observed in relation to a specific site. SMRs for lung cancer was higher among ever exposed to bitumen than among unexposed. There was no association between lung cancer risk and estimated exposure to bitumen fume, and no dose-response was apparent. CONCLUSIONS: While the results of this cohort study indicate a slightly increased SMR for lung cancer, it did not produce evidence of a causal link between lung cancer and exposure to bitumen fume.

Adult↗

Stage II malignant melanoma: presentation of a prognostic model and an assessment of specific active immunotherapy in 1,273 patients.

The ability to redefine risk factors and to predict prognosis in patients with malignant melanoma at the time they manifest nodal metastasis can be a benefit to the patient emotionally and to the physician therapeutically. A retrospective review of 1,273 patients with stage II malignant melanoma was performed at our institution. The most significant prognostic factors in a simultaneous hazard Cox multivariate analysis, predicting melanoma-related mortality among stage II patients, were the number of positive nodes (P less than 0.0001), age (P = 0.0004), site of the primary lesion (P = 0.0036), disease-free interval (P = 0.016), thickness of the primary lesion (P = 0.017), and sex of the patient (P = 0.0616). We have developed a model for predicting survival of stage II patients, designed for use in the clinic setting. Its application in a computer system makes it accessible and understandable. The most favorable risk group (18% of the population) has actuarial 5- and 10-year survival rates of 58% and 49%, respectively, from the time of the nodal metastasis. The least favorable risk group (7% of the population) has 5- and 10-year survival rates of 15% and 10%, respectively. There are three intermediate risk groups. All groups differ prognostically (P less than 0.04). The principal adjuvant therapy offered to these patients was specific active immunotherapy, which appears to have a 10-20% survival benefit in stage II patients with greater than one positive node, when compared with institutional controls. The apparent survival benefit of the immunotherapy supports continued clinical investigation of its therapeutic potential.

Actuarial Analysis↗

A statistical test of compatibility of data sets to a common dose-response model.

Quantitative estimates of cancer risk generally involve low-dose extrapolation based on an exponential dose-response model for dichotomous response data. Frequently more than one data set is available. If a careful analysis of the biological issues indicates that more than one of the available data sets could be used in the quantitative estimate of cancer risk, it is reasonable to think of combining the data. Before combining data, however, it would be prudent to test whether the data sets are compatible with a common dose-response model. If they are not, it could be concluded that an underlying biological factor is responsible. If they are statistically compatible, the decision to combine data sets based on biological issues would be reinforced. A statistical test based on the generalized likelihood ratio method is proposed for evaluating the compatibility of different data sets with a common dose-response model. This method of constructing a statistical test and the associated asymptotic theory is consistent with the approach used by GLOBAL86 (R. B. Howe, K. S. Crump, and C. Van Landingham, GLOBAL86: A Computer Program to Extrapolate Quantal Animal Toxicity Data to Low Doses, K. S. Crump & Co., Ruston, LA, 1986) for estimating the confidence limits that are used as a basis for quantitative estimates.

Animals↗

Ratio of branched chain amino acid to tyrosine after hepatectomy.

The roles of branched chain amino acids (BCAAs) and the tyrosine (Tyr) profile after liver resection were investigated using an inexpensive enzymatic method that was recently developed to quantify their concentrations. The preoperative BCAAs-to-Tyr ratio (BTR) was significantly correlated with the preoperative indocyanin green clearance ratio. The BTR decreased immediately after surgery in all patients, but it was significantly lower in those who had undergone major hepatectomies. After the infusion of BCAA-enriched amino acid solution, the BTR increased substantially, being significantly higher in patients who had not suffered an elevation in total bilirubin after liver resection. These findings indicate that this new enzymatic method to quantify the concentration of BCAAs and Tyr is useful to control the infusion of amino acids and to study the role of amino acid metabolization during the perioperative period.

Amino Acids, Branched-Chain↗

Calculation of the 1995 lung cancer incidence in The Netherlands and Sweden caused by smoking and radon: risk implications for radon.

A two-mutation carcinogenesis model was used to calculate the expected lung cancer incidence caused by both smoking and exposure to radon in two populations, i.e. those of the Netherlands and Sweden. The model parameters were taken from a previous analysis of lung cancer in smokers and uranium miners and the model was applied to the two populations taking into account the smoking habits and exposure to radon. For both countries, the smoking histories and indoor radon exposure data for the period 1910-1995 were reconstructed and used in the calculations. Compared with the number of lung cancer cases observed in 1995 among both males and females in the two countries, the calculations show that between 72% and 94% of the registered lung cancer cases may be attributable to the combined effects of radon and smoking. In the Netherlands, a portion of about 4% and in Sweden, a portion of about 20% of the lung cancer cases (at ages 0-80 years) may be attributable to radon exposure, the numbers for males being slightly lower than for females. In the Netherlands, the proportions of lung cancers attributable to smoking are 91% for males and 71% for females; in Sweden, the figures are 70% and 56%, respectively. The risk from radon exposure is dependent on gender and cigarette smoking: the excess absolute risk for continuous exposure to 100 Bq m-3 ranges between 0.003 and 0.006 and compares well with current estimates, e.g. 0.0043 of the International Commission on Radiological Protection (ICRP). The excess relative risk for continuous exposure to 100 Bq m-3 shows a larger variation, ranging generally between 0.1 for smokers and 1.0 for non-smokers. The results support the assumption that exposure to (indoor) radon, even at a level as low as background radiation, causes lung cancer proportional to the dose and is consistent with risk factors derived from the miners data.

Adult↗

Lung cancer in nuclear workers of Mayak. A comparison of numerical procedures.

Lung cancer mortality was analyzed among 4279 nuclear workers of the Mayak facilities in the former Soviet Union, who were exposed to chronic irradiation both externally and internally from incorporated plutonium. The analysis was carried out in terms of a relative risk model. It was shown that an earlier estimate of the excess relative risk for lung cancer, that exceeds the value employed by ICRP by a factor of roughly 2, as well as an earlier estimated latency period of 24 years for lung cancer induction were the result of the numerical procedure chosen. In another recently published case control study, a purely quadratic, threshold-type dose response to incorporated plutonium was deduced. In the present calculations, no evidence for a departure from linearity in dose response was suggested. Principal aim of this study has been the comparison to methods used in the earlier cohort analysis. More detailed risk modelling on the basis of the most recent follow-up will be required.

Colorado↗