The objectives of this project are to identify and describe determinants of cancer in the United States through analytical, biostatistical, and epidemiologic approaches. Continuing investigation in several areas of the United States has shown that most esophageal cancer in blacks and whites is explained by cigarette smoking and alcohol consumption. The rapid rise of adenocarcinoma of the esophagus may be partially explained by obesity and gastroesophageal reflux, but no excesses were associated with use of prescription H2 antagonists or anticholinergic drugs. Approximately one quarter of pancreatic cancer cases among whites and blacks are due to cigarette smoking, but regular consumption of alcohol was not linked with this malignancy. Excesses of renal cell carcinoma were linked with hypertension and medications used to treat this disorder (though it was difficult to disentangle the effects of the disease from the treatments), and with dietary protein consumption, high parity among women, cigarette smoking, and obesity. In a case-control study of renal pelvis and ureter cancer, no association was found for lifetime cumulative ingestion or duration of use of phenacetin, aspirin, or acetaminophen. In ongoing analyses of rare cancers, oral contraceptives were linked with elevated risk of adrenocortical cancer among women and cigarette smoking with increased risk of extrahepatic bile cancer and adrenocortical cancer in men. Extrahepatic bile cancer was also associated with obesity, and male breast cancer with heavy body mass index and lack of exercise. Among healthy adults, neopterin and B2- microglobulin levels increased with age and were higher among whites than blacks and among males than females. In a collaborative study with the Radiation Epidemiology Branch, data collection is ongoing to assess the possible role of cellular telephones in occurrence of adult brain tumors and the relationship of power frequency electromagnetic fields, radon, and other environmental exposures with childhood acute lymphoblastic leukemia. Analysis of data from a case-control study of oral cancer in Puerto Rico has begun.