Shu-Xiang Yao

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 Peoples 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.

Serum tocopherols, selenium and lung cancer risk among tin miners in China

AbstractObjective: To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case–control study nested in an occupational cohort of tin miners. Methods: Male workers free of cancer enrolled in the cohort. During up to 6 years of follow-up, 339 lung cancer cases were diagnosed and, among these cases, those who donated blood prospectively (n = 108) were eligible for this study. For each case, two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection. Results: Overall, we observed no association between serum alpha-tocopherol, gamma-tocopherol or selenium levels and lung cancer risk. However, a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60years old (odds ratio by tertile: 1.0, 0.9, 0.2; trend p = 0.002). Alpha-tocopherol was also protective in men who reported no alcohol drinking (OR by tertile: 1.0, 0.6, 0.3; trend p = 0.008). Conclusion: Although there were no significant overall associations between prospectively collected serum alpha-tocopherol, gamma-tocopherol or selenium and incidence of lung cancer, results from this study suggest that higher alpha-tocopherol levels may be protective in men less than 60 years old and in those who do not drink alcohol.

Risk factors and early detection of lung cancer in a cohort of Chinese tin miners.

PURPOSE To examine risk factors and establish a biologic specimen and data bank for the study of early markers of lung cancer. METHODS We designed a dynamic cohort using an ongoing lung cancer screening program among radon- and arsenic-exposed tin miners in Yunnan China. Through the first four years of the study, 8,346 miners aged 40 years and older with over 10 years of occupational exposure have been enrolled, risk factors have been assessed, annual sputum and chest radiographs have been obtained, and numerous biologic specimens have been collected. RESULTS A total of 243 new lung cancer cases have been identified through 1995. Radon and arsenic exposures are the predominant risk factors, but lung cancer risk is also associated with chronic bronchitis and silicosis, as well as a number of exposure to tobacco smoke, including early age of first use, duration, and cumulative exposure. Tumor and sputum samples are being examined for early markers of lung cancer. CONCLUSION A cohort of occupationally-exposed tin miners with an extensive biologic specimen repository has been successfully established to simultaneously study the etiology and early detection of lung cancer.

Association Between Sputum Atypia and Lung Cancer Risk in an Occupational Cohort in Yunnan, China

BACKGROUND Individuals with cytologic atypia in sputum may be at high risk for the development of lung cancer. METHODS A prospective cohort study was conducted among occupational tin miners in Yunnan, China, based on an annual lung cancer screening program. Sputum samples were collected prospectively at baseline and the following seven annual screenings. The associations between risk factors and sputum cytology were analyzed by univariate and multivariate logistic regression. A proportional hazard model was used to analyze the association between the baseline sputum results and the incidence of lung cancer. The effect of consecutive sputum cytology on the increase of lung cancer risk was analyzed by logistic regression. RESULTS Sputum cytologic atypia was associated with age, smoking, occupational radon and arsenic exposure, and asthma. Sputum cytologic atypia was an independent risk factor for lung cancer with an adjusted hazard ratio (HR) of 3.82 (95% confidence interval [CI], 2.82 to 5.18) in comparing normal to moderate or worse atypia. Compared to the lung cancer risk associated with normal sputum, the risk was significantly higher according to the degree of atypia for squamous carcinomas, small cell lung cancer and central lung cancer, with adjusted HRs of 5.70 (95% CI, 3.78 to 8.59), 3.32 (95% CI, 1.31 to 8.45), and 4.93 (95% CI, 3.51 to 6.92), respectively. CONCLUSIONS Sputum atypia is associated with an increased risk of lung cancer. Sputum cytologic examination combined with other screening examinations may play an important role in the early detection of lung cancer or in the selection of the optimal target population for more intensive lung cancer screening among this occupational cohort or similar population.

Prior lung disease and lung cancer risk in an occupational-based cohort in Yunnan, China

We used the data from a prospective cohort study among tin miners in Yunnan, China to investigate whether prior lung disease is a risk factor for lung cancer. Information on prior lung disease was obtained from baseline questionnaires. The Cox proportional hazards model was used to examine the relationship between prior lung disease and lung cancer risk. From 1992 to 2001, a total of 502 lung cancer cases were confirmed among 9295 cohort participants. Prior chronic bronchitis was associated with an increase in lung cancer risk with an adjusted HR of 1.50 (95% CI: 1.24-1.81). There was an increased risk of developing squamous cell carcinoma in the setting of prior chronic bronchitis and small cell carcinoma in association with asthma with an adjusted HRs of 1.57 (95% CI: 1.19-2.09) and 2.56 (95% CI: 1.38-4.75), respectively. This prospective study provides further evidence that prior chronic bronchitis correlates with increased lung cancer risk, especially for squamous cell carcinoma. Asthma is associated with increased risk of small cell lung carcinoma.

Season‐specific Correlation between Dietary Intake of Fruits and Vegetables and Levels of Serum Biomarkers among Chinese Tin Miners at High Risk for Lung Cancer

M.R. FORMAN,a,h J. ZHANG,b E. GUNTER,c S.X. YAO,b M. GROSS,d Y.L. QIAO,e B.I. GRAUBARD,f P.R. TAYLOR,a S. KEITH,g AND M. MAHERa aCancer Prevention Studies Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20892-7058, USA bLabor Protection Institute, Yunnan Tin Mine Corporation, Gejiu, Yunnan, PR China cNHANES Laboratory of Biochemical Analyses, Centers for Disease Prevention and Control, Atlanta, Georgia, USA dDepartment of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA eDepartment of Cancer Epidemiology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing 100002 1, PR China fBiostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA gInformaiton Management Sciences, Silver Spring, Maryland, USA

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; β-carotene, 50 mg; vitamin E, 800 IU; and selenium, 400 μg) were administered daily with placebos to 350 miners according to a 24 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.

Modification of association between prior lung disease and lung cancer by inhaled arsenic: A prospective occupational-based cohort study in Yunnan, China

Arsenic and prior lung diseases have been shown to increase lung cancer risk; however, little is known about their joint effects. The aim of our study was to analyze the joint effects of inhaled arsenic and prior lung diseases on lung cancer risk within a occupational cohort. The interactions of prior lung diseases and inhaled arsenic were analyzed based on multiplicative and additive scales in the Cox proportional hazards model. Compared with low arsenic exposure and no history of asthma, the hazard ratios (HRs) of high arsenic exposure with asthma, high arsenic exposure without asthma and low arsenic exposure with asthma were 2.61 (95% CI: 1.71–4.00), 2.60 (95% CI: 1.93–3.51) and 2.49 (95% CI: 1.53–4.06), respectively. Based on the multiplicative scale in the Cox proportional hazards model, the HR of the interaction of asthma and arsenic on lung cancer risk was 0.45 (95% CI: 0.25–0.80). Based on the additive scale, the relative excess risk due to interaction between asthma and arsenic was −1.41 (95% CI: −2.81 to −0.02). Our study provides strong evidence that arsenic exposure is associated with lung cancer risk. A significant negative interaction between asthma and arsenic on lung cancer risk is observed.

Retrospective analysis of screening results of lung cancer cases among occupational population at high risk of lung cancer

BACKGROUND Lung cancer has become the leading cause of the cancer death in China. Population-based lung cancer screening is still in controversy. The objective of this study is to analyze the effect of annual chest radiography and sputum cytological screening conducted in high lung cancer risk population who were exposed to work related carcinogens. METHODS A retrospective analysis was conducted to evaluate the screening results of the lung cancer cases diagnosed from 1992 to 2001 in the miners of Yunnan tin mine. RESULTS A total of 9317 miners had been screened annually from 1992 to 1999. A total of 46 779 chest radiography and 45 672 sputum cytological examinations had been conducted, and 793 cohort subjects had at least one positive result. The annual positive detection rate ranged from 1214.1/100 000 to 3482.7/100 000. By December 31, 2001, 433 lung cancer cases had been confirmed, 371 cases out of them had cytological/pathological evidence, and 55.0% were squamous cell carcinoma followed by adenocarcinoma and small cell carcinoma. Stage I or II accounted for 24%. 62.1% of the cases had at least one positive screening result, while 165 cases were detected by chest radiography alone, 56 were detected by sputum cytology, and 48 were detected by both screening modalities. 64.2% of X-ray detected cases were squamous/adenous carcinomas and 75.0% of cytological detected cases were squamous carcinoma. 80.8% of early stage cases had at least one previous positive finding from screening. CONCLUSIONS Annual lung cancer screening with combination of chest radiography and sputum cytology play some extent role in early detection of lung cancer in high risk population. The results may provide some primary data for lung cancer screening in special population who are at high risk of lung cancer in China.

Establishment of cohort to study lung cancer in Yunnan tin miners

BACKGROUND To establish a cohort for the study of risk factors of lung cancer, and to support the study of early biomarkers and prevention of lung cancer. METHODS Designed a special population-based prospectively dynamic cohort among radon- and arsenic-exposed tin miners aged 40 or more years old with at least 10 years of occupational exposure in Yunnan Province, P.R.China. The mass screenings with sputum cytology and chest X-ray were conducted annually. The baseline information was collected for assessing demographic characteristics and risk factors. The multiple sputum specimens, chest radiographs and numerous biologic specimens have been collected and stored. RESULTS From 1992-1999, 9143 miners have been enrolled and 460 new cases of lung cancer have been found. There had 47655 person-time chest radiographs and 46625 person-time sputum cytology among the cohort in 8 years. The relative risks of age-adjusted exposure to chronic bronchitis, silicosis, and tobacco were 1.73, 1.46, and 1.32 respectively. CONCLUSIONS A cohort of unique occupationally-exposed tin miners with an extensive biologic specimen repository and data bank has been successfully established. Although occupational exposures are the predominant risk factors among the high risk miners, lung cancer risk is also associated with chronic obstructive lung disease (chronic bronchitis and silicosis) and a number of measures of exposure to tobacco smoke, including early age of first use, duration, and cumulative exposure.