Project 3: Arsenic Biomarker Epidemiology


Arsenic is ranked number one on the Superfund Priority List of Hazardous Substances. During the last five years, we have found that early life exposure to arsenic results in major mortality increases among young adults aged 30-49 from lung cancer and bronchiectasis, myocardial infarction, kidney cancer, and bladder cancer. Our Chile studies have recently identified even more causes of death related to arsenic, and show that peak mortality risks are much greater than those from any other environmental exposure anywhere in the world. We plan to continue our investigation of arsenic exposure and mortality in northern Chile for the years 1950 to 2000, now assessing mortality due to pulmonary tuberculosis, chronic renal failure, and our newly discovered evidence of increased mortality from cancers of the larynx, penis, cervix and thyroid gland. We will also follow a unique cohort of children in Bangladesh who were highly exposed to arsenic in utero and in early childhood, including measuring lung function, assessing the incidence of chronic respiratory disease and upper respiratory tract infections, measuring blood pressure, blood glucose and β2-microglobulin, a marker of reduced kidney glomerular filtration rate. We will collect urine samples and buccal cells from Bangladesh and from our ongoing northern Chile early life exposure study, to analyze epigenetic alterations and proteomic biomarkers of arsenic exposure, susceptibility, and disease. We will use the northern Chile buccal and urine samples to assess the impact on pulmonary function and respiratory symptoms in adults, decades after high exposure. We will conduct in vitro studies to determine the mechanism and downstream effects involved in the persistent down-regulation of HBD1 gene expression by the toxic arsenic metabolite, MMA3. We will also knock down HBD1 gene expression in target organ cell lines to determine the genes that are affected by HBD1 down-regulation. In summary, we are proposing an integrated research strategy assessing multiple outcomes from arsenic exposure in population studies, focusing on effects from early life exposure, along with pursuing evidence concerning mechanisms of action.

This is relevant because arsenic is present in many Superfund sites. We have shown marked increases in mortality among adults following early life exposure for several causes of death, with mortality increases much greater than from any other known environmental exposure. In our proposed new work, we will investigate new findings following childhood exposure, and will study the mechanisms of action by which arsenic produces them.

Project Leadership

Allan H. Smith, MD, PhD

Professor of Epidemiology

Director, Arsenic Health Effects Research Program
Epidemiology, School of Public Health
University of California, Berkeley

Martyn T. Smith, PhD

Professor of Toxicology

Environmental Health Sciences,
School of Public Health
University of California, Berkeley

Craig T. Steinmaus, MD, MPH

Associate Adjunct Professor

Epidemiology, School of Public Health
University of California, Berkeley

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Selected Publications


Steinmaus CM (2016) Perchlorate in Water Supplies: Sources, Exposures, and Health Effects. Curr Environ Health Rep. Jun;3(2):136-43. PMCID: PMC4834222. [PDF]

Carlos-Wallace FM, Zhang L, Smith MT, Rader G, Steinmaus C (2016) Parental, In Utero, and Early-Life Exposure to Benzene and the Risk of Childhood Leukemia: A Meta-Analysis. Am J Epidemiol. Jan 1;183(1):1-14. PMCID: PMC4751231. [PDF]


Steinmaus C, Castriota F, Ferreccio C, Smith AH, Yuan Y, Liaw J, Acevedo J, Pérez L, Meza R, Calcagno S, Uauy R, Smith MT (2015) Obesity and excess weight in early adulthood and high risks of arsenic-related cancer in later life. Environ Res. Oct;142:594-601. PMCID: PMC4664040. [PDF]

Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC (2015) Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Persp. Feb;124(2):170-5. PMID: PMC4749078. [PDF]


Smith AH, Marshall G, Yuan Y, Steinmaus C, Liaw J, Smith MT, Wood L, Heirich M, Fritzemeier RM, Pegram MD, Ferreccio C (2014) Rapid reduction in breast cancer mortality with inorganic arsenic in drinking water. EBioMedicine. Nov;1(1):58-63. PMCID: PMC4286879. [PDF]

Steinmaus C, Ferreccio C, Yuan Y, Acevedo J, González F, Perez L, Cortés S, Balmes JR, Liaw J, Smith AH (2014). Elevated Lung Cancer in Younger Adults and Low Concentrations of Arsenic in Water. Am J Epidemiol. Dec 1;180(11):1082-87. PMCID: PMC4239797. [PDF]

Steinmaus C, Ferreccio C, Acevedo J, Yuan Y, Liaw J, Durán V, Cuevas S, García J, Meza R, Valdés R, Valdés G, Benítez H, VanderLinde V, Villagra V, Cantor KP, Moore LE, Perez SG, Steinmaus S, Smith AH (2014) Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure. Cancer Epidemiol Biomarkers Prev. Aug;23(8):1529-38. PMCID: PMC4344186. [PDF]

Melak D, Ferreccio C, Kalman D, Parra R, Acevedo J, Pérez L, Cortés S, Smith AH, Yuan Y, Liaw J, Steinmaus C (2014) Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile. Toxicol Appl Pharmacol. Jan 15;274(2):225-31. PMCID: PMC4344188. [PDF]

Kalman DA, Dills RL, Steinmaus C, Yunus M, Khan AF, Prodhan MM, Yuan Y, Smith AH (2014) Occurrence of trivalent monomethyl arsenic and other urinary arsenic species in a highly exposed juvenile population in Bangladesh. J Expo Sci Environ Epidemiol. Mar-Apr; 24(2):113-20. PMID: 23549402. DOI: 10.1038/jes.2013.14 [PDF]


Smith AH, Yunus M, Khan AF, Ercumen A, Yuan Y, Hira-Smith M, Liaw J, Balmes J, von Ehrenstein O, Raqib R, Kalman D, Alam DS, Streatfield PK, Steinmaus C (2013) Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh. Int J Epidemiol. Aug;42(4):1077-1086. PMCID: PMC3781005. [PDF]

Ferreccio C, Yuan Y, Calle J, Benítez H, Parra RL, Acevedo J, Smith AH, Liaw J, Steinmaus C (2013) Arsenic, tobacco smoke, and occupation: associations of multiple agents with lung and bladder cancer. Epidemiology. Nov;24(6):898-905, 2013. PMID: 24036609. DOI: 10.1097/EDE.0b013e31829e3e03. [PDF]

Ferreccio C, Smith AH, Durán V, Barlaro T, Benítez H, Valdés R, Aguirre JJ, Moore LE, Acevedo J, Vásquez MI, Pérez L, Yuan Y, Liaw J, Cantor KP, Steinmaus C (2013) Case-control study of arsenic in drinking water and kidney cancer in uniquely exposed northern Chile. Am J Epidemiol. Sep 1;178(5):813-818. PMCID: PMC3817454. [PDF]

Steinmaus C, Ferreccio C, Romo JA, Yuan Y, Cortes S, Marshall G, Moore LE, Balmes JR, Liaw J, Golden T, Smith AH (2013) Drinking water arsenic in northern Chile: high cancer risks 40 years after exposure. Cancer Epidemiol Biomarkers. Apr;22(4)623-30. PMCID: PMC3848421. [PDF]

Dangleben NL, Skibola CF, Smith MT (2013) Arsenic immunotoxicity: a review. Environ Health. Sep 2;12(1):73. PMCID: PMC3848751.

Herceg Z, Lambert MP, van Veldhoven K, Demetriou C, Vineis P, Smith MT, Straif K, Wild CP (2013) Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation. Carcinogenesis. Sep;34(9):1955-67. PMCID: PMC3765050.


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]


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]


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]


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]


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]


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]


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]


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]