Risk factors for cancer from the ambient environment are studied to identify specific chemicals and classes of contaminants, to investigate mechanisms of action, and to estimate the contribution of environmental factors to cancer in the general population. Case-control studies are conducted on non-Hodgkin's lymphoma and cancers of the lung, bladder, colon, rectum, stomach, esophagus, brain, pancreas, and kidney. Exposures include drinking water contaminants, especially disinfection byproducts and arsenic; airborne radon in homes; and body burdens of chlorinated hydrocarbons from past environmental or dietary exposures. Related case-control studies in Iowa showed excess risks for rectal cancer in both sexes and bladder and brain cancers among men after long-term consumption of disinfection byproducts in drinking water. The risk of brain cancer after such exposures is being further investigated in the upper midwest as is lung cancer risk in Iowa. We earlier found an association between PCBs in stored serum and subsequent risk of non-Hodgkin's lymphoma. Recent work showed that the higher-chlorinated congeners as well as certain immunotoxic congener groups were most strongly associated with risk of NHL. Further analyses showed no association with several other organochlorines. Studies in Taiwan, Chile, and Argentina have described a high risk for bladder and other cancers after exposure to arsenic in drinking water supplies at levels several times the maximum contaminant limit. A case-control study in northern New England is evaluating bladder risk at lower levels of arsenic that are more common in the U.S. A case-control study of lung cancer and residential radon among Missouri women is unique because it used a novel radon detector which integrates residential radon exposure over the past 30 years (CR-39 detector). A significant excess lung cancer risk was observed with increasing radon concentrations when measure by the CR-39 detector but not when measured by standard radon dosimetry. We are further validating the Iowa and Missouri glass dosimetry technique by exposing the dosimeters to glass objects in homes in Minnesota and Finland that have had radon measurements made every year for the past 15 years. Pathology and epidemiology data from the Iowa and Missouri radon studies will be combined for a pooled analysis. Analysis of the interaction of radon with genetic polymorphisms is anticipated. K-Ras mutations were elevated among female lung cancer patients exposed to unvented coal smoke in China. Among healthy women exposed to smoky coal emissions, mutations in the p53 gene, and to a lesser extent, the K-ras gene, were elevated in non-malignant epithelial cells taken from the sputum. Further results suggested that single nucleotide polymorphisms in the oxidative stress related-genes AKR1C3 and OGG1 may play a role in the pathogenesis of lung cancer in this population. A retrospective cohort study of licensed radio amateurs, including an occupational component, is evaluating patterns of mortality that may be related to hobby or workplace exposures. Several activities are developing new approaches, and improving existing methods, of exposure assessment in studies of general environmental exposures. These are required to better estimate risk and to detect the relatively small increases in risk often encountered in such studies. Databases of water contaminants, gathered for routine monitoring purposes, are being used to estimate past exposures to subjects in case-control studies.