Project 3: Arsenic Biomarker Epidemiology
Summary
Presentation: Overview of Project 3
Millions of people are exposed to arsenic-contaminated water in the U.S. and worldwide, and arsenic is ranked first on the most recent priority list of Superfund site hazardous substances. Current evidence suggests that lung cancer is the leading cause of arsenic-associated mortality. In addition, arsenic also increases the incidence of non-malignant pulmonary disease, and intriguing preliminary evidence obtained by this research group suggests that those exposed as young children or in utero are particularly susceptible to both the malignant and non-malignant pulmonary effects of arsenic. This project is undertaking a series of investigations to further explore the effects of childhood arsenic exposure and the mechanisms that may confer susceptibility to these effects. The epidemiological studies include a case-control study of childhood and in utero arsenic exposure and subsequent risks of lung cancer in young adults in Northern Chile, and a cross-sectional study of lung function and respiratory health and arsenic exposure involving children in West Bengal. In addition, biological samples collected during these studies, combined with samples collected from several past studies, are being used for additional investigations on 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. Project investigators have an additional new focus on the respiratory effects of childhood and in utero exposures and the associated mechanisms of toxicity and susceptibility. Given the widespread exposure to ingested arsenic in the U.S. and worldwide, and the very high risks of lung disease following early life exposures seen in preliminary studies, investigating these effects has the potential to yield important new public health and scientific information regarding the in utero and childhood effects of toxic substances.
News
In a recent study, Dr. Allan Smith’s group compared lung cancer risks from inhalation and ingestion of arsenic. For more information, see: [PDF]
Dr. Allan Smith has received the John Goldsmith Award for Outstanding Contributions to Environmental Epidemiology at the International Society for Environmental Epidemiology meeting in Dublin. For more information, please see: http://www.iseepi.org/about/awards.html
Martyn Smith is a panelist in a session entitled “Human Carcinogen Risk” which is part of a Workshop on “Genomics in Cancer Risk Assessment” at the 10th Annual International Conference on Environmental Mutagens, August 20 – 28, 2009 in Venice, Italy. For more information, click here
Events
No events at this time.
Project Update
Arsenic is ranked first on the most recent priority list of Superfund site hazardous substances. In addition, millions of people are exposed to arsenic through naturally contaminated groundwater. This project explores the effects of childhood arsenic exposure and the mechanisms that may confer susceptibility to these effects.
Drs. Allan Smith and Martyn Smith have continued their investigations of early life exposure to arsenic in studies in Chile and Bangladesh. In Chile, they have continued a lung cancer case-control study, which includes interviewing patients with lung cancer who had exposure to high concentrations of arsenic in their drinking water when they were young children. Subjects from unexposed regions who have been diagnosed with lung cancer at young ages are also included. Data on arsenic exposure, occupational history, smoking status and diet are being collected in cases and age- and gender- matched controls. In Bangladesh the researchers have continued their study of lung function in arsenic-exposed children. Earlier studies in West Bengal, India showed major lung function deficits in adults with evidence of high arsenic exposure. In this new investigation, they are now investigating if these lung function changes also occur in children. The group has been very pleased with the quality of spirometry their collaborators are achieving in the field.
Several studies have shown that susceptibility to arsenic could be related to how well people metabolize or methylate arsenic. In both the Chile and Bangladesh study they are investigating susceptibility related to methylated forms of arsenic in urine samples with collaborators at the University of Washington. New methods to detect the highly unstable metabolite of arsenic (MMA3) are being developed. MMA3 is highly toxic in vitro and some data suggests it could be the primary toxic species. Levels of MMA3 and other arsenic forms will be assessed in both the Chile and Bangladesh studies.
During 2008 the researchers reported their findings concerning mortality from childhood liver cancer in northern Chile for children who have high exposure to arsenic in early life. Those exposed as young children had a ten-fold increase in liver cancer mortality.
Publications
- » Jo WJ, Loguinov A, Wintz H, Chang M, Smith AH, Kalman D, Zhang L, Smith MT, Vulpe CD (2009) Comparative Functional Genomic Analysis Identifies Distinct and Overlapping Sets of Genes Required for Resistance to Monomethylarsonous Acid (MMAIII) and Arsenite (AsIII) in Yeast. Toxicol Sci. 111(2), 424-436. PMID: 19635755. PMCID: PMC274584. [Abstract] [Full text]
- Lan, Qing, Luoping Zhang, Min Shen, William J. Jo, Roel Vermeulen, Guilan Li, Christopher Vulpe, Sophia Lim, Xuefeng Ren, Stephen M. Rappaport, Sonja I. Berndt, Meredith Yeager, Jeff Yuenger, Richard B. Hayes, Martha S. Linet, Songnian Yin, Stephen Chanock, Martyn T. Smith, and Nathaniel Rothman. 2009. Large-scale evaluation of candidate genes Identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity. Carcinogenesis. (http://carcin.oupjournals.org/)
30(1):50-58. doi:10.1093/carcin/bgn249 (http://dx.doi.org/10.1093/carcin/bgn249) - Scelo, Ghislaine, Catherine Metayer, L. Zhang, Joseph L. Wiemels, Melinda C. Aldrich, Steve Selvin, Stacy Month, M.T. Smith, and Patricia A. Buffler. 2009. Household exposure to paint and petroleum solvents, chromosomal translocations, and the risk of childhood leukemia. Environmental Health Perspectives. 117(1):133-9. doi:10.1289/ehp.11927 (http://dx.doi.org/10.1289/ehp.11927)
- Smith, Allan H. and Craig Murray Steinmaus. 2009. Health Effects of Arsenic and Chromium in Drinking Water: Recent Human Findings. Annual Review of Public Health. 30(9):1-9. doi:10.1146/annurev.publhealth.031308.100143 (http://dx.doi.org/10.1146/annurev.publhealth. 031308.100143)
- Smith, Allan H., A. Ercumen, Yan Yuan, and Craig Murray Steinmaus. 2009. Increased Lung Cancer Risks are Similar Whether Arsenic is Ingested or Inhaled. Journal of Exposure Science and Environmental Epidemiology. (http://www.nature.com/jes/index.html) 19:343-348. doi:10.1038/jes.2008.73 (http://dx.doi.org/10.1038/jes.2008.73)