Quantitative evaluation of the radon and lung cancer association in a case control study of Chinese tin miners.

Studies of underground miners have consistently shown an increased risk of lung cancer with cumulative exposure to radon-222 and its decay products. Although the deleterious effects of high radon exposure are clear, questions regarding the shape of the exposure-response relationship, and the effects of time factors such as attained age, time since exposure and early age at first exposure, the effect of exposure rate, and the joint association of radon exposure and tobacco use have not yet been fully clarified. This report considers these questions by fitting various models for the relative odds of disease to 74 male lung cancer cases who were diagnosed between 1981 and 1984 and were alive in 1985 and an equal number of controls. All subjects are current or past employees of the Yunnan Tin Corporation, Gejiu City, China, who reside in the local area. Workers were interviewed to obtain information on work history, from which radon exposure in cumulative working level months and arsenic exposure were estimated, and on tobacco use. Results indicate that excess relative risk increases by 1.7% per cumulative working level month [95% confidence interval (0.5, 5.4)]. The linear exposure response relationship significantly declines with year since last radon exposure (P = 0.02). The risk trend also declines with increasing exposure rate (P = 0.001), indicating that long duration of exposure at a low rate may be more deleterious than short duration of exposure at a high rate. A unique aspect of this study population is the very early ages at first radon exposure for many of the workers, about 37% of the radon-exposed workers were first exposed under the age of 13 years. The analysis shows no modification of the radon lung cancer relationship with age at first exposure. These patterns of risk with radon exposure are generally consistent with those reported in the recent National Academy of Sciences' Biological Effects of Ionizing Radiations IV report. The primary method of tobacco consumption in this area of China is by waterpipe. Lung cancer risk increases with pipe-years of use. The joint analysis of tobacco use and radon exposure supports the Biological Effects of Ionizing Radiations IV conclusion that the most likely model is between additive and multiplicative. The variations of the radon lung cancer relationship by years since last exposure and exposure rate are not affected by adjustment for arsenic exposure.

The effect of dietary intake of fruits and vegetables on the odds ratio of lung cancer among Yunnan tin miners.

All newly diagnosed cases of lung cancer (N = 183) among male tin miners of Yunnan Province, China and age-sex matched occupational controls (N = 183 aged 45-79 years) were interviewed within 3 months following cancer diagnosis. The questionnaire included information about usual adult diet as well as employment and smoking histories. Over 95% of cases and controls were current smokers. The 27-item food frequency questionnaire included 11 fruits and vegetables rich in vitamin A and/or carotenoids. The effect of dietary intake of fruits and vegetables on risk of lung cancer was examined with adjustment for exposures to radon, arsenic, and smoking as previously documented risk factors for lung cancer. Tin miners with reduced intake of yellow and light green vegetables had statistically significant increased odds ratios (OR) of lung cancer (OR = 2.26 and OR = 2.39 for the lowest two quartiles of intake; P value for trend = 0.02) among cases compared with controls after multiple logistic regression adjustment for covariates; and this relationship was monotonic. Tin miners with reduced intake of tomatoes had statistically significant increased adjusted OR of lung cancer (OR = 2.64, OR = 3.09, OR = 2.36 for the three lowest quartiles of intake; P value for trend = 0.04). This is the first study to demonstrate a protective effect of vegetable intake versus the strong effects of smoking and occupational exposures on lung cancer risk.

A study on acid-base disturbance in patients with post-traumatic multiple organ failure.

In order to diagnose accurately the type of acid-base disturbance (ABD) in patients with post-traumatic multiple organ failure (PMOF), arterial blood gases and electrolytes were determined 645 times on 112 patients with PMOF and the data were analyzed with the pre-estimated compensatory formula of ABD and the calculations of anion gap, potential bicarbonate, and blood chlorides. Simple ABD was found in 381 times of determinations and double ABD in 239 when only the formula was used in the analysis, while 264 times of simple ABD, 260 times of double ABD and 96 times of triple ABD were found when the formula was employed in combination with the calculations of anion gap, potential bicarbonate and blood chloride. The mixed types of ABD were increased by 49% (117 times) from 239 to 356 times and triple ABD was increased from 0 to 96 times. The findings indicate that the employment of the combined formula and the calculations of anion gap, potential bicarbonate and blood chloride is of great significance to assess ABD especially its mixed and complicate types in patients with PMOF. It is emphasized that along with the monitoring of blood gases, the determination of blood electrolytes and the calculation of anion gap and potential bicarbonate should be performed to determine the correct type of ABD.

Intervention trial with selenium for the prevention of lung cancer among tin miners in Yunnan, China. A pilot study.

This pilot study evaluated the feasibility and effectiveness of conducting a double-blind clinical trial for the prevention of lung cancer with selenium (Se) in Yunnan Tin Corporation, the People's Republic of China, where the incidence rates of lung cancer are extraordinarily high among the miners. Forty healthy miners were randomized to either 300 micrograms of Se in high Se malt cakes or an identical placebo of malt cakes daily for one year. Subjects consumed their usual daily diet. The low Se concentrations in plasma (0.05 +/- 0.008 microgram/mL) and hair (0.442 +/- 0.085 microgram/g) reflected their low dietary Se intake in the control subjects. In Se-supplemented group, the Se status was increased by 178% for serum and 194.8% for hair. The serum GSHpx activity was increased by 155.7%, whereas the lipid peroxide level was reduced by 74.5% compared to the placebo. The results of UDS assay indicated that the lymphocyte DNA damage induced by ultraviolet irradiation and carcinogen 3,4-benzpyrene could be protected by Se supplementation. Se-supplementation did not affect the liver function test (SGPT), as well as the concentrations of hemoglobin, albumin, and cholesterol. Thus, daily intake of 300 micrograms Se in form of Se-malt as a chemopreventive measure is safe and effective to humans with low Se status.

[Sister chromatid exchanges (SCE), chromosomal aberrations and micronuclei of cultured peripheral lymphocytes in patients with lung cancer, miners and non-mining workers of the tin mine in Yunnan].

Determination of SCE frequency, chromosomal aberration and micronucleus rate of cultured peripheral lymphocytes in 32 patients with lung cancer, 33 miners and 40 non-mining workers in Yunnan Tin Mine was carried out. The results showed that the cancer patients had higher SCE incidence, chromosomal aberration and micronucleus rate, the non-mining workers had the least and miners on an intermediate level. There was a significant difference of SCE, chromosomal aberrations and micronucleus rate between patients and non-mining workers (P less than 0.05-0.01). We also found that miners had a significant higher SCE and chromosomal aberration rate but not micronucleus rate as compared with the non-mining workers. We proposed that some carcinogens present in the Yunnan Tin Mine be responsible for the genetic damages in the miners. Chemical drugs may be considered to contribute to the genetic damage in cancer patients who had a tendency toward an increased SCE, chromosomal aberration and micronucleus rate as compared to the miners, though without reaching a statistical significance. We suggested that combination assay of SCE with chromosomal aberration or micronucleus be an useful index for screening of the high risk population and monitoring the chemical drug prevention of lung cancers in Yunnan Tin Mine.

[Experimental research on the pathogenic mechanisms in adult respiratory distress syndrome].

In order to study the pathogenic mechanisms of adult respiratory distress syndrome (ARDS), the neutrophil aggregation activity, platelet aggregation rate and levels of thromboxane, prostacyclin, superoxide dismutase, lipoperoxides, neutrophil elastase, alpha 1-antitrypsin and angiotensin conversion enzyme were measured in 84 experimental dogs. Under the action of activated complement C5a, polymorphonuclear leukocyte aggregation with increased release of oxygen radicals play an important role in the pathogenesis of ARDS.

[The role of oxygen radicals in adult respiratory distress syndrome].

A traumatic adult respiratory distress syndrome (ARDS) model was made with 3 intravenous bolus of homologous bone marrow extract in rabbits. Variables were then measured including the metabolites of oxygen radicals in plasma and expired gases, serum lactic dehydrogenase (LDH) isoenzymes and plasma fibronectin (Fn). A two peak increase was found in expired ethane and plasma conjugated dienes following decrease of periphery white blood and polymorphonuclear neutrophil (PMN) differential count; continuous increase of serum LDH3 and severe descent of plasma Fn were also found after the trauma. The above results suggest that PMN releasing oxygen radicals play an important role in RDS pathogenesis; and expired ethane, circulating conjugated dienes, LDH3 and Fn may be useful for making diagnosis and prognosis assessment of ARDS.

[Effects of pentoxifylline on leukocyte in the lungs of dog with fat tissue extract-induced respiratory distress syndrome].

We studied the effects of pentoxifylline (PTX) on the polymorphonuclears (PMN) and alveolar macrophages (AM) in the lung of dog with fat tissue extract induced respiratory distress syndrome (RDS). Results showed that PTX decreased PMN accumulation and infiltration in the lung; the total leukocytes in BALF dropped from 2.92 x 10(8) in the experimental group to 1.21 x 10(8) in the PTX-treated group (P < 0.001); the percentage of PMN also reduced from 35.4% to 14.3% (P < 0.01); the production of IL-1 and TNF by AM in the PTX-treated group was markedly inhibited as compared with the experimental group (P < 0.001, P < 0.05). We conclude that PTX has an inhibitory effect on PMN and AM in the lung of dog with RDS, and PTX may have potential therapeutic effect on ARDS.

[Effect of pentoxifylline on respiratory distress syndrome in dogs].

We examined effects of early post-treatment with pentoxifylline (PTX) on fat tissue extract (FTE) induced respiratory distress syndrome in dogs. The results indicate that the arterial oxygen tension in the animals received PTX dropped more slowly, the total leukocytes and albumin in BALF were obviously reduced, the increased production of IL-1 and TNF by alveolar macrophages was partly inhibited, other parameters such as W/D ratio were also markedly decreased when compared to the animals received FTE only. PTX decreases neutrophil accumulation and prevents the increase in pulmonary vascular permeability, and attenuates edema formation in FTE-induced lung injury. The mechanism may relate with the effect of PTX inhibiting inflammatory leukocytes and protecting the pulmonary vascular endothelial cells.

Relation of arsenic exposure to lung cancer among tin miners in Yunnan Province, China.

The relation of mining and smelting exposure to arsenic and lung cancer was studied among tin miners in Yunnan Province in the People's Republic of China. Interviews were conducted in 1985 with 107 living tin miners who had lung cancer and an equal number of age matched controls from among tin miners without lung cancer to obtain information on risk factors for lung cancer including detailed history of employment and tobacco use. Occupational history was combined with industrial hygiene data to estimate cumulative arsenic exposure. Similar methods were also used to estimate radon exposure for simultaneous evaluation in this analysis. The results indicate that subjects in the highest quarter of cumulative arsenic exposure have a relative risk of 22.6 compared with subjects without exposure after adjusting for tobacco and radon exposure, and a positive dose response relation was observed. Simultaneous evaluation of arsenic and tobacco exposure indicates a greater risk for arsenic, whereas simultaneous assessment of arsenic and radon exposure suggests radon to be the greater risk. There is no evidence of synergism between arsenic and tobacco exposure. Among arsenic exposed individuals, cases of lung cancer have longer duration but lower average intensity of arsenic exposure than controls, indicating that duration of exposure to arsenic may be more important than intensity in the aetiology of lung cancer. Finally, risk of lung cancer among workers exposed to arsenic only in mining is only slightly less than for miners whose exposure to arsenic was limited to smelting, although risks are highest when workers were exposed to both mining and smelting.

Relation of radon exposure and tobacco use to lung cancer among tin miners in Yunnan Province, China.

We studied the relation of radon exposure and tobacco use to lung cancer among tin miners in Yunnan Province in the People's Republic of China. Interviews were conducted in 1985 with 107 living tin miners with lung cancer and an equal number of age-matched controls from among tin miners without lung cancer to obtain information on lung cancer risk factors including a detailed history of employment and tobacco use. Occupational history was combined with extensive industrial hygiene data to estimate cumulative working level months (WLM) of radon daughter exposure. Similar data were also used to estimate arsenic exposure for control in the analysis. Results indicate an increased risk of lung cancer for water pipe smoking, a traditional form of tobacco use practiced in 91% of cases and 85% of controls. Ever use of water pipes was associated with a twofold elevation in risk when compared with tobacco abstainers, and a dose-response relation was observed with increasing categories of pipe-year (dose times duration) usage. Estimated WLM of radon exposure varied from 0 to 1,761 among subjects but averaged 515 in cases versus only 244 in controls. Analyses indicated that the persons in the highest quarter of the radon exposure distribution had an odds ratio (OR) = 9.5 (95% confidence interval = 2.7-33.1) compared to persons without radon exposure after controlling for arsenic exposure and other potential confounders. Examination of duration and rate of radon exposure indicated higher risk associated with long duration as opposed to high rate of exposure. Cross-categorizations of radon exposure and tobacco use suggest greater risk associated with radon exposure than tobacco in these workers.

Dietary determinants of lung-cancer risk: results from a case-control study in Yunnan Province, China.

The relation between diet and lung cancer was studied among male residents of a mining community in Yunnan Province. After obtaining food frequency data from subjects or proxies, we compared diets of 428 cases, aged 35-74 years, and 1,011 age-matched controls. Cases tended to consume slightly more rice, but less protein-rich foods (i.e., bean curd, meat, eggs) and vegetables than did controls. The relative risks of lung cancer across increasing quartiles of meat (i.e., pork) consumption, for example, were 1.00, 0.67, 0.72 and 0.46 (p for trend less than 0.01). The relative risks of lung cancer across increasing quartiles of consumption of dark-green, leafy vegetables were 1.00, 0.62, 0.52 and 0.41 (p for trend less than 0.01). Although specific dietary constituent(s) responsible for the protective effect of vegetable consumption could not be identified, carotenoids other than beta-carotene, or compounds in cruciferous or Allium vegetables, are possibilities.

Feasibility of conducting a lung-cancer chemoprevention trial among tin miners in Yunnan, P. R. China.

Tin miners in Yunnan Province in southern China have an extremely high rate of lung cancer, more than one percent per year among those at 'high risk' (40+ years old, with 10+ years of underground mining and/or smelting experience). The extraordinary lung cancer rates result from combined exposure to radon, arsenic, and tobacco smoking (cigarettes and/or bamboo water pipe). A study to determine the feasibility of conducting a large-scale, lung-cancer chemoprevention trial was conducted in 1986 among currently employed or retired miners from the Yunnan Tin Corporation in the city of Gejiu. The study was designed to answer four questions: (i) Could potentially eligible miners be identified and recruited? (ii) Could intervention agents be shipped successfully from the United States to the study area and be appropriately distributed? (iii) Would miners adequately adhere to the study protocol and comply with the intervention regimen? (iv) Could potential adverse effects be monitored and documented? The six-month feasibility study yielded affirmative answers to each of these questions. A roster of over 7,000 high-risk miners was compiled. Four agents (vitamin A, 25,000 IU; beta-carotene, 50 mg; vitamin E, 800 IU; and selenium, 400 micrograms) were administered daily with placebos to 350 miners according to a 2(4) factorial design. Adherence, assessed by pill counts and serum micronutrient levels, was approximately 90 percent. The findings from this preliminary study indicate that a full-scale, lung-cancer chemoprevention trial in this population is feasible.