The overall goal of this project is to identify strategies to reduce lung cancer incidence and mortality. Specific objectives are to 1) establish a biologic specimen bank and data bank that can be used for the validation and refinement of potential early markers of lung cancer and 2) establish a cohort for the study of environmental (including dietary) and genetic risk factors for lung cancer. BACKGROUND: Lung cancer is the leading cause of cancer death in the U.S. While relative survival rates for localized disease are dramatically better than for nonlocalized disease, most patients are not diagnosed early enough for present therapies to be effective, and early detection by screening with conventional modalities (i.e., chest x-ray and/or sputum cytology) has not been shown to be beneficial. Potential strategies to reduce the incidence and mortality of lung cancer include new methods of early detection, and identification and alteration of etiologic factors. METHODS: Miners in the Yunnan Tin Corporation have an extraordinary rate of lung cancer due to exposure to radon, arsenic, and tobacco. Over 7000 high-risk miners (40+ years old with 10+ years of underground and/or smelting experience)have been the target of an annual lung cancer screening program (CXR and sputum cytology)for the past 20+ years. Between 1992 and 1999 sputum samples were collected and stored annually for future early marker research, and new cases of lung cancer ascertained. Prediagnostic sputum and other biologic samples are stored for analysis for potential early markers (e.g., biochemical, molecular or monoclonal antibody markers) utilizing a nested case-control approach. PROGRESS: Over 450 lung cancer were identified through 1999 in this cohort. Analyses to date have evaluated occupational exposures (arsenic and radon), smoking, and medical conditions; a number of serum antioxidants (carotenoids, selenium, tocopherols); and one potential marker in sputum (Mab 703D4 in the detection of hnRNP). New follow-up has been initiated to update vital and cancer status through 2005. New studies initiated in the YTC cohort include: (i) an analysis of serologic markers of HPV infection in relation to lung cancer; (ii) studies of the microbiome in sputum samples collected as part of the YTC lung cancer screening to include evaluation of the relation of the microbiome to lung cancer etiology, early detection, and environmental and occupational exposures (tobacco, radon, arsenic); and (iii) a pilot study to compare DNA alterations in sputum and tumors in lung cancer cases.