Interaction of radiation and smoking in lung cancer induction among workers at the Mayak nuclear enterprise.
ABSTRACT For radiation-related cancer risk evaluation, it is important to assess not only influences of individual risk factors but also their interactive effects (e.g., additive, multiplicative, etc.). Multivariate analysis methods adapted for interactive effects allow such assessments. We have used a multivariate analysis approach to investigate the pair-wise interactions of the previously identified three main etiological factors for lung cancer induction in Russian workers of the Mayak Production Association (PA) nuclear enterprise. These three factors are as follows: (1) body burden of inhaled plutonium-239 (239Pu), an influence on absorbed alpha-radiation dose; (2) cumulative, absorbed external gamma-radiation dose to the lung; and (3) level of cigarette smoking as indicated by a smoking index (SI). The SI represents the cigarettes smoked per day times years smoking. The Mayak PA workers were exposed by inhalation to both soluble and insoluble forms of 239Pu. Based on a cohort of 4,390 persons (77% male), we conducted a nested, case-control study of lung cancer induction using 486 matched cases and controls. Each case was matched to two controls. Matching was based on five factors: sex, year of birth, year work began, profession, and workplace. Three levels of smoking were considered: low (SI = 1 to 499), used as a reference level; middle (SI = 500 to 900); and high (SI = 901 to 2,000). For lung cancer induction, a supra-multiplicative effect was demonstrated for high external gamma-ray doses (> 2.0 Gy) plus high 239Pu intakes (body burden >2.3 kBq). This observation is consistent with the hypothesis of curvilinear dose-response relationships for lung cancer induction by high- and low-LET radiations. The interaction between radiation (external gamma rays or 239Pu body burden) and cigarette smoke was found to depend on the smoking level. For the middle level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with additive effects. However, for the high level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with the occurrence of multiplicative effects. These results indicate that low-dose risk estimates for radiation-induced lung cancer derived without adjusting for the influence of cigarette smoking could be greatly overestimated. Further, such systematic error may considerably distort the shape of the risk vs. dose curve and could possibly obscure the presence of a dose threshold for radiation-induced lung cancer.
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ABSTRACT: In a retrospective study, we investigated lung-cancer mortality from 1951 to 1976 in 1415 Swedish iron miners exposed to short-lived radioactive daughters of radon gas at concentrations leading to annual doses close to the currently accepted occupational limit. Fifty deaths from lung cancer were observed, as compared with 12.8 expected; expected rates were determined by a smoking-specific analysis based on data from a random sample of the Swedish male population. Among nonsmokers 18 deaths were observed, as compared with 1.8 expected; among current smokers and recent exsmokers 32 deaths were observed and 11.0 were expected. The effects of smoking and exposure to alpha radiation from radon daughters were nearly additive. Comparison of lung-cancer risk coefficients from this study and from other cohort studies of underground miners showed good agreement. Exposure to radon daughters is a major medical problem is underground metal mining, but our results also indicate that exposure to radon daughters at home accounts for an appreciable number of cases of lung cancer in the general population.New England Journal of Medicine 07/1984; 310(23):1485-94. · 51.66 Impact Factor
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ABSTRACT: This article documents the study of 383 cases of lung cancer in uranium miners and presents for the first time the relationship of radioactive radon gas and cigarette smoking. There is evidence that alpha radiation from radon gas at exposure levels above 465 working level months (WLM) is a strong contributor to the development of lung cancer. Cigarette smoking plays the most significant role in causing lung tumor; this is also noticed in nonminers who smoke cigarettes. A synergistic or additive effect of these two carcinogens is strongly suggested. The data indicate that small cell tumors develop in younger nonsmoking miners exposed to radon levels above 465 WLM. Lung cancers develop in smoking miners at lower levels of radon exposure than in nonsmoking miners. Based on an average mining experience of 15 years, there is substantial evidence that the present maximum allowable limit of 0.3 working levels (WL), or 4 working level months (WLM) per year, is safe, representing a margin of safety of approximately 10:1. Furthermore, a comparison of these data with the radon levels in some homes, averaging in the neighborhood of 0.025 WL, would indicate that health risks at these levels are negligible. It is suggested that 20 picocuries/liter, which equals 0.10 WL, be the maximum allowable level in homes.Cancer 11/1988; 62(7):1402-8. · 5.20 Impact Factor
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ABSTRACT: Genomic instability is characterized by the increased rate of acquisition of alterations in the mammalian genome. These changes encompass a diverse set of biological end points including karyotypic abnormalities, gene mutation and amplification, cellular transformation, clonal heterogeneity and delayed reproductive cell death. The loss of stability of the genome is becoming accepted as one of the most important aspects of carcinogenesis, and the numerous genetic changes associated with the cancer cell implicate genomic stability as contributing to the neoplastic phenotype. Multiple metabolic pathways govern the accurate duplication and distribution of DNA to progeny cells; other pathways maintain the integrity of the information encoded by DNA and regulate the expression of genes during growth and development. For each of these functions, there is a normal baseline frequency at which errors occur, leading to spontaneous mutations and other genomic anomalies. This review summarizes the current status of knowledge about radiation-induced genomic instability. Those events and processes likely to be involved in the initiation and perpetuation of the unstable phenotype, the potential role of epigenetic factors in influencing the onset of genomic instability, and the delayed effects of cellular exposure to ionizing radiation are discussed.Radiation Research 10/1996; 146(3):247-58. · 2.70 Impact Factor