Chile

Incident Cancer Studies in a Unique Arsenic-Exposed Area of Chile
(Grant: # R01ES014032 )  Publications
Steinmaus, Craig M (craigs@uclink.berkeley.edu ) - University of California Berkeley
Abstract: Despite a recent lowering of the US arsenic drinking water standard, millions of people in the US continue to be exposed to drinking water arsenic, and the cancer risks associated with these exposures could be very high, especially in susceptible subpopulations. Current US arsenic regulations do not incorporate information on potentially susceptible subgroups. However, we have identified new ecologic evidence that arsenic exposure during childhood or in utero could cause a 13-fold increase in lung cancer mortality in young adults, compared to a 3-4 fold increase caused by exposure occurring later in life. We have also found evidence that people producing high levels of monomethylated arsenic (MMA) have bladder cancer risks that are 2-5 times higher than others, perhaps due to the highly toxic trivalent form (MMA3). Importantly, the data on these potential susceptible subgroups are preliminary and need to be confirmed. The unique arsenic exposed population in Northern Chile offers an excellent opportunity to investigate these effects. Because almost all of the population in Northern Chile has obtained their drinking water from large municipal sources, and past arsenic levels in these sources are well documented, arsenic carcinogenicity can be studied using exposure data that are much more accurate than can be obtained anywhere else in the world. In addition, a distinct period of very high exposure in this area has created a population where tens of thousands of people were exposed to high arsenic levels only in utero or as young children, and tens of thousands of people were exposed only as adults, offering an extremely rare opportunity to study the long term impacts of early life carcinogen exposure. We propose a case-control study of 675 cases of lung and bladder cancer obtained over a three-year period using a rapid case ascertainment system involving all local pathologists. Controls will be obtained from the Chile electoral register containing 94% of the Chilean population. Biological samples and dietary information will be collected on all subjects. The information gained from this project may help to determine if there are susceptible groups, such as children, those who metabolize arsenic poorly, or those with poor nutrition, who may need special consideration in regulatory standard setting. Information on MMA3 and diet, and the future genetic and proteomic studies we plan to develop in this investigation, could add further insight into the co-factors and mechanisms of arsenic carcinogenesis.

Toxic Substances in the Environment
(Grant: # P42ES004705 )  Publications
Smith, Martyn T (martynts@berkeley.edu ) - University of California Berkeley
Abstract: The goal of the Superfund Basic Research Program at the University of California, Berkeley is ""to improve understanding of the relationship between exposure and disease; provide better human and ecological risk assessments; lower cleanup costs; and develop a range of prevention strategies to improve and protect public health, ecosystems and the environment."" The Program builds on the strengths of UC Berkeley and Lawrence Berkeley National Laboratory in engineering, chemistry and molecular epidemiology, and consists of six interrelated basic and applied research projects. The overall theme of the program is ""The application of functional genomics, proteomics, transcriptomics, and nanotechnology to better detect arsenic, mercury, benzene, polycyclic aromatic hydrocarbons, trichloroethylene and other Superfund priority chemicals in the environment; evaluate their effects on human health, especially the health of susceptible populations such as children; and remediate their presence and reduce their toxicity. Themes of the individual projects include using proteomics and transcriptomics to study the role of chemical exposure in causing childhood leukemia; taking a functional genomic approach to finding susceptibility genes; applying novel biomarkers to study the health effects of arsenic; improving bioremediation of toxic chemicals through the application of -omic technologies and nanotechnology, and developing nano-scale sensors of chemical species in the environment. A toxicogenomic laboratory core and a computational biology core will assist researchers in creating tools for use in epidemiological and risk research. The new research translation core will facilitate intensive discussions between investigators and government audiences, and generate new initiatives to increase understanding of the significance and applicability of emerging areas of research to public health protection through policy, interventions, and individual actions. The training core will prepare graduate and post-doctoral students to conduct multidisciplinary research into the effects of environmental factors on health, and to develop technological solutions to prevent or mitigate the harm resulting from Superfund priority chemicals. CHILE - The study being conducted in Chile is a case-control study of childhood and in utero arsenic exposure and subsequent risks of lung cancer in young adults. Samples collected for this study include water samples and urine. In addition, detailed questionnaires will be completed. The biological samples collected will be used to investigate arsenic susceptibility and mechanisms of toxicity including: 1). Susceptibility related to individual differences in urinary concentrations of MMA3, a highly toxic but rarely studied arsenic metabolite; 2). Susceptibility related to genetic polymorphisms, in particular those involving AS3MT (cyt19), GSTO1, GSTM1, and EGFR. 3). Assessment of urinary proteomic patterns as biomarkers of exposure, disease, and susceptibility. INDIA - The study in West Bengal India will involve a cross-sectional study of lung function and respiratory health and arsenic in children. Lung function will be assessed in the children by non-invasive spirometry. Samples to be collected include urine and water. In addition an extensive questionnaire will be administered. The biological samples collected will be used to investigate arsenic susceptibility and mechanisms of toxicity including: 1). Susceptibility related to individual differences in urinary concentrations of MMA3, a highly toxic but rarely studied arsenic metabolite; 2). Susceptibility related to genetic polymorphisms, in particular those involving AS3MT (cyt19), GSTO1, GSTM1, and EGFR. 3). Assessment of urinary proteomic patterns as biomarkers of exposure, disease, and susceptibility.