Project 3: Arsenic Biomarker Epidemiology

Summary

audio_icon pdf_icon2 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

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Project Update

Investigators from the Superfund Research Program at Berkeley have contributed greatly to our understanding of the many diseases and disorders caused by arsenic.  They were the first to discover that exposure to arsenic in childhood causes disease later in life, an example of a critical window for exposure.  Dr. Allan Smith and his colleagues have also worked tirelessly to acquaint public health and governmental officials with the importance of taking actions to control arsenic in drinking water around the world, giving many presentations every year and serving on expert committees.  Arsenic contaminates groundwater in many countries, including parts of the U.S.

Overall goals
Investigators are conducting epidemiology studies in several countries around the world and using advanced methods including biological markers of human exposure (such as arsenic metabolites in the urine) in order to:

  1. learn more about what diseases are caused or worsened by arsenic exposure;
  2. better understand the critical windows of exposure to arsenic during early life and childhood and the concentrations or doses of arsenic that cause disease.
  3. find out how arsenic acts in the body to causes diseases.

Important discoveries so far

  1. Early life exposure to arsenic, even at relatively low levels, causes disease in adulthood more than 30 years later.  This finding was first reported by Superfund researchers at Berkeley.
  2. Arsenic exposure contributes to susceptibility to tuberculosis.  This finding was first reported by Superfund researchers at Berkeley.

Highlight for last year
The most important things we discovered over the last year were that death from tuberculosis is more likely following arsenic exposure.  This is a novel finding.  A paper on this is in press in the American Journal of Epidemiology.

What we plan to do next
Investigators will continue their studies in Chile and Bangladesh to find out how early life exposure to arsenic causes disease during adulthood.

In Chile, investigators are looking at people who were exposed to arsenic in drinking water during childhood to see if they are more likely to develop lung cancer as adults.  This “case-control” study is collecting data on arsenic exposure, occupational history, smoking status and diet for people who have the disease (cases) and others who are matched by age and gender (controls).

In Chile, investigators are also starting to study lung function, using a technique called “spirometry.”  This study will determine if those with early life exposure to arsenic have reduced lung function many years later.

In Bangladesh, investigators have already collected data for their study of lung function in children who were exposed to arsenic. Their earlier studies in West Bengal, India, showed major lung function deficits in adults with evidence of high arsenic exposure. In this new study, they are now investigating if these lung function deficits also occur in children.  The next thing they will do is to analyze their data.

In another line of research, investigators are considering how arsenic causes adverse effects and why these may be different for different people.  Some people appear to be more susceptible to arsenic.  Past research suggests that this greater susceptibility to arsenic may be related to how well people metabolize or methylate arsenic. In both the Chile and Bangladesh study, we are investigating susceptibility related to methylated forms of arsenic in urine samples with our collaborators at the University of Washington.

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Selected Publications

2012

  • Smith AH, Marshall G, Liaw J, Yuan Y, Ferreccio C, Steinmaus C (2012) Mortality in Young Adults following in Utero and Childhood Exposure to Arsenic in Drinking Water. Environ Health Perspect. Nov;120(11):1527-31. PMCID: PMC3556614. [PDF]
  • Smith AH and Steinmaus CM (2011) Arsenic in drinking water. BMJ. May 5;342:d2248. PMID: 21546418. (PMC Journal – In Process). [PDF]
  • Smith AH, Liaw J, Steinmaus C (2012) Relationship of Creatinine and Nutrition with Arsenic Metabolism: Smith et al. Respond. Environ Health Perspect. Apr 1;120(4):a146-a147. PMCID: PMC3339472. [PDF]

2011

  • Basu A, Mitra S, Chung J, Guha Mazumder DN, Ghose N, Kalman DA, von Ehrenstein OS, Steinmaus C, Liaw J, Smith AH (2011) Creatinine, Diet, Micronutrients, and Arsenic Methylation in West Bengal, India. Environ Health Perspect. Jun 7(Epub ahead of print). PMID: 21652291. [PDF]
  • Smith AH, Marshall G, Yuan Y, Liaw J, Ferreccio C, Steinmaus C (2011) Evidence from Chile that arsenic in drinking water may increase mortality from pulmonary tuberculosis. Am J Epidemiol. Feb 15;173(4):414-20. PMID: 21190988. [PDF]

2010

  • Steinmaus C, Smith AH, Smith MT (2010) Regarding “Meta-analysis and Causal Inference: A Case Study of Benzene and Non-Hodgkin Lymphoma”: An Incomplete Analysis. Ann Epidemiol. Aug 11. [Epub ahead of print] PMID: 20705482. [PDF]
  • Porter KE, Basu A, Hubbard AE, Bates MN, Kalman D, Rey O, Smith A, Smith MT, Steinmaus C, Skibola CF (2010) Association of genetic variation in cystathionine-beta-synthase and arsenic metabolism. Environ Res. Aug;110(6):580-7. PMCID: PMC2913479. [PDF]
  • Steinmaus C, Yuan Y, Kalman D, Rey OA, Skibola CF, Dauphine D, Basu A, Porter KE, Hubbard A, Bates MN, Smith MT, Smith AH (2010) Individual differences in arsenic metabolism and lung cancer in a case-control study in Cordoba, Argentina. Toxicol Appl Pharmacol. Sep 1;247(2):138-45. PMID: 20600216. [PDF]
  • Schwilk E, Zhang L, Smith MT, Smith AH, Steinmaus C (2010) Formaldehyde and leukemia: an updated meta-analysis and evaluation of bias. J Occup Environ Med. Sep;52(9):878-86. PMID: 20798648. [PDF]
  • Ren X, McHale CM, Skibola CF, Smith AH, Smith MT, Zhang L (2010) An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis. EHP. Aug 2 [Epub ahead of print]. doi: 10.1289/ehp.1002114. [PDF]
  • Yuan Y, Marshall G, Ferreccio C, Steinmaus C, Liaw J, Bates M, Smith AH (2010) Kidney cancer mortality: fifty-year latency patterns related to arsenic exposure. Epidemiology. Jan; 21(1):103-8. PMID: 20010213. [PDF]

2009

  • Steinmaus C, Yuan Y, Liaw J, Smith AH (2009) Low-level population exposure to inorganic arsenic in the United States and diabetes mellitus: a reanalysis. Epidemiology. Nov; 20(6):807-15. PMID: 19652600. [PDF]
  • 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. Oct; 111(2):424-36. PMID: 19635755. PMCID: PMC2742584. [PDF]
  • Smith AH, Ercumen A, Yuan Y, Steinmaus CM (2009) Increased lung cancer risks are similar whether arsenic is ingested or inhaled. J Expo Sci Environ Epidemiol. May; 19(4):343-8. PMID: 19190673. PMCID: PMC2682945. [PDF]
  • Smith AH, Steinmaus CM (2009) Health effects of arsenic and chromium in drinking water: recent human findings. Annu Rev Public Health. Apr 29; 30(107-22. PMID: 19012537. PMCID: PMC2762382. [PDF]
  • Rahman A, Vahter M, Smith AH, Nermell B, Yunus M, El Arifeen S, Persson LA, Ekstrom EC (2009) Arsenic exposure during pregnancy and size at birth: a prospective cohort study in Bangladesh. Am J Epidemiol. Feb 1; 169(3):304-12. PMID: 19037006. [PDF]

2008

  • Hegedus CM, Skibola CF, Warner M, Skibola DR, Alexander D, Lim S, Dangleben NL, Zhang L, Clark M, Pfeiffer RM, Steinmaus C, Smith AH, Smith MT, Moore LE (2008) Decreased urinary beta-defensin-1 expression as a biomarker of response to arsenic. Toxicol Sci. Nov; 106(1):74-82. PMID: 18511430. PMCID: PMC2563143. [PDF]
  • Liaw J, Marshall G, Yuan Y, Ferreccio C, Steinmaus C, Smith AH (2008) Increased childhood liver cancer mortality and arsenic in drinking water in northern Chile. Cancer Epidemiol Biomarkers Prev. Aug; 17(8):1982-7. PMID: 18708388. PMCID: PMC2694756. [PDF]
  • Steinmaus C, Smith AH, Jones RM, Smith MT (2008) Meta-analysis of benzene exposure and non-Hodgkin lymphoma: biases could mask an important association. Occup Environ Med. Jun; 65(6):371-8. PMID: 18417556. [PDF]
  • Smith AH (2008) Hexavalent chromium, yellow water, and cancer: a convoluted saga. Epidemiology. Jan; 19(1):24-6. PMID: 18091414. [PDF]

2007

  • Yuan Y, Marshall G, Ferreccio C, Steinmaus C, Selvin S, Liaw J, Bates MN, Smith AH (2007) Acute myocardial infarction mortality in comparison with lung and bladder cancer mortality in arsenic-exposed region II of Chile from 1950 to 2000. Am J Epidemiol. Dec 15; 166(12):1381-91. PMID: 17875584. [PDF]
  • Thundiyil JG, Yuan Y, Smith AH, Steinmaus C (2007) Seasonal variation of arsenic concentration in wells in Nevada. Environ Res. Jul; 104(3):367-73. PMID: 17459366. [PDF]
  • Marshall G, Ferreccio C, Yuan Y, Bates MN, Steinmaus C, Selvin S, Liaw J, Smith AH (2007) Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. J Natl Cancer Inst. Jun 20; 99(12):920-8. PMID: 17565158. [PDF]
  • Smith MT, Jones RM, Smith AH (2007) Benzene exposure and risk of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. Mar; 16(3):385-91. PMID: 17337645. [PDF]
  • Steinmaus C, Moore LE, Shipp M, Kalman D, Rey OA, Biggs ML, Hopenhayn C, Bates MN, Zheng S, Wiencke JK, Smith AH (2007) Genetic polymorphisms in MTHFR 677 and 1298, GSTM1 and T1, and metabolism of arsenic. J Toxicol Environ Health A. Jan 15; 70(2):159-70. PMID: 17365577. [PDF]
  • Hira-Smith MM, Yuan Y, Savarimuthu X, Liaw J, Hira A, Green C, Hore T, Chakraborty P, von Ehrenstein OS, Smith AH (2007) Arsenic concentrations and bacterial contamination in a pilot shallow dugwell program in West Bengal, India. J Environ Sci Health A Tox Hazard Subst Environ Eng. Jan; 42(1):89-95. PMID: 17129953. [PDF]
  • von Ehrenstein OS, Poddar S, Yuan Y, Mazumder DG, Eskenazi B, Basu A, Hira-Smith M, Ghosh N, Lahiri S, Haque R, Ghosh A, Kalman D, Das S, Smith AH (2007) Children’s intellectual function in relation to arsenic exposure. Epidemiology. Jan; 18(1):44-51. PMID: 17149142. [PDF]

2006

  • Von Ehrenstein OS, Jenny AM, Basu A, Smith KR, Hira-Smith M, Smith AH (2006) Capacity building in environmental health research in India and Nepal. Int J Occup Environ Health. Oct-Dec; 12(4):300-6. PMID: 17168216. [PDF]
  • Savarimuthu X, Hira-Smith MM, Yuan Y, von Ehrenstein OS, Das S, Ghosh N, Mazumder DN, Smith AH (2006) Seasonal variation of arsenic concentrations in tubewells in west Bengal, India. J Health Popul Nutr. Sep; 24(3):277-81. PMID: 17366769. [PDF]
  • Smith AH, Marshall G, Yuan Y, Ferreccio C, Liaw J, von Ehrenstein O, Steinmaus C, Bates MN, Selvin S (2006) Increased mortality from lung cancer and bronchiectasis in young adults after exposure to arsenic in utero and in early childhood. Environ Health Perspect. Aug; 114(8):1293-6. PMID: 16882542. PMCID: PMC1551995. [PDF]
  • George CM, Smith AH, Kalman DA, Steinmaus CM (2006) Reverse osmosis filter use and high arsenic levels in private well water. Arch Environ Occup Health. Jul-Aug; 61(4):171-5. PMID: 17867571. [PDF]
  • Chung JS, Haque R, Guha Mazumder DN, Moore LE, Ghosh N, Samanta S, Mitra S, Hira-Smith MM, von Ehrenstein O, Basu A, Liaw J, Smith AH (2006) Blood concentrations of methionine, selenium, beta-carotene, and other micronutrients in a case-control study of arsenic-induced skin lesions in West Bengal, India. Environ Res. Jun; 101(2):230-7. PMID: 16332366. [PDF]
  • Steinmaus CM, George CM, Kalman DA, Smith AH (2006) Evaluation of two new arsenic field test kits capable of detecting arsenic water concentrations close to 10 microg/L. Environ Sci Technol. May 15; 40(10):3362-6. PMID: 16749706. [PDF]
  • Steinmaus C, Bates MN, Yuan Y, Kalman D, Atallah R, Rey OA, Biggs ML, Hopenhayn C, Moore LE, Hoang BK, Smith AH (2006) Arsenic methylation and bladder cancer risk in case-control studies in Argentina and the United States. J Occup Environ Med. May; 48(5):478-88. PMID: 16688004. [PDF]
  • von Ehrenstein OS, Guha Mazumder DN, Hira-Smith M, Ghosh N, Yuan Y, Windham G, Ghosh A, Haque R, Lahiri S, Kalman D, Das S, Smith AH (2006) Pregnancy outcomes, infant mortality, and arsenic in drinking water in West Bengal, India. Am J Epidemiol. Apr 1; 163(7):662-9. PMID: 16524957. [PDF]

2005

  • Mazumder DN, Steinmaus C, Bhattacharya P, von Ehrenstein OS, Ghosh N, Gotway M, Sil A, Balmes JR, Haque R, Hira-Smith MM, Smith AH (2005) Bronchiectasis in persons with skin lesions resulting from arsenic in drinking water. Epidemiology. Nov; 16(6):760-5. PMID: 16222165. [PDF]
  • Steinmaus CM, Yuan Y, Smith AH (2005) The temporal stability of arsenic concentrations in well water in western Nevada. Environ Res. Oct; 99(2):164-8. PMID: 16194666. [PDF]
  • von Ehrenstein OS, Mazumder DN, Yuan Y, Samanta S, Balmes J, Sil A, Ghosh N, Hira-Smith M, Haque R, Purushothamam R, Lahiri S, Das S, Smith AH (2005) Decrements in lung function related to arsenic in drinking water in West Bengal, India. Am J Epidemiol. Sep 15; 162(6):533-41. PMID: 16093295. [PDF]
  • Steinmaus C, Carrigan K, Kalman D, Atallah R, Yuan Y, Smith AH (2005) Dietary intake and arsenic methylation in a U.S. population. Environ Health Perspect. Sep; 113(9):1153-9. PMID: 16140620. PMCID: PMC1280394. [PDF]
  • Steinmaus C, Yuan Y, Kalman D, Atallah R, Smith AH (2005) Intraindividual variability in arsenic methylation in a U.S. population. Cancer Epidemiol Biomarkers Prev. Apr; 14(4):919-24. PMID: 15824164. [PDF]
  • Moore LE, Pfeiffer R, Warner M, Clark M, Skibola C, Steinmous C, Alguacil J, Rothman N, Smith MT, Smith AH (2005) Identification of biomarkers of arsenic exposure and metabolism in urine using SELDI technology. J Biochem Mol Toxicol. 19(3):176. PMID: 15977200. [PDF]

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