Cancer in adults following in utero and early life exposure to arsenic. We propose to investigate whether early-life or in utero exposure to arsenic could result in increased cancer risks more than 40 years after exposure reduction. To do this, we seek to continue our successful case-control study of early-life arsenic exposure and cancer in northern Chile, with new aims on cancer in older age groups and on breast and prostate cancer. In utero and childhood exposures may affect adult cancer risks, but few studies have examined this issue primarily due to difficulties in assessing past exposure. A unique situation in Chile in which tens of thousands of people were exposed to high arsenic drinking water concentrations in utero and as children from 1958-70, with good data on exposure, provides a rare opportunity to investigate the long- term early-life effects of arsenic. Using this natural experiment, we identified novel findings on lung and bladder cancer latency, kidney cancer, low exposures, arsenic metabolism, important co-exposures, and susceptibility. We also found rare human evidence that an in utero and childhood chemical exposure can cause major increases in adult lung cancer decades after high exposures were stopped (odds ratios of 5.6 (1.1-27.8) for in utero and 4.7 (2.6-8.5) for childhood exposure). But, because of the timing of the high exposure (1958-70) and the timing of our study (2007-10), the impacts of in utero or childhood exposure could only be assessed in adults up to about ages 50 and 65, respectively. By continuing this study we will be able to see whether these astonishing effects continue into older age groups (i.e., 60-75 years old), including those ages where cancer is most common and where public health impacts would be greatest. Growing in vitro and human evidence also suggests that arsenic may decrease breast cancer and increase prostate cancer risks. Arsenic is used to treat some rare cancers, and causes breast cancer cell apoptosis and re-expression of estrogen-receptor. It also causes malignant transformation of prostate stem cells, overexpression of prostate specific antigen, and androgen independence in prostate cancer cells. We identified ecological evidence in Chile that arsenic led to major reductions in breast cancer (RR=0.36;0.24-0.55) and major increases in prostate cancer (RR=3.97;1.08-10.2). Further investigation showed confounding was unlikely, but findings were ecologic and must be confirmed. In our study, we will collect detailed data on lifetime exposure and confounders, and biologic samples from 350 lung, 250 bladder, 450 breast, and 350 prostate cancer cases and 1000 controls in northern Chile. We seek to perform the first human study of a common in utero and childhood exposure and adult cancer in those ages where cancer is most common, and the first prostate and breast cancer studies with good data on lifetime arsenic exposure. Relatively little is known about the impacts of environmental chemicals on prostate or breast cancer risks, or the long-term cancer risks of early-life exposure. The importance of this project lies in the millions of people in the US exposed to arsenic, and the possibility that these exposures, especially in early-life or in utero, could increase cancer risks, even many decades after exposures occurred.

Public Health Relevance

Millions of people in the US and worldwide are exposed to arsenic in contaminated water and food, and these exposures could be associated increased cancer risks. This project seeks to evaluate whether people exposed to arsenic as fetuses or young children, or people with other potential susceptibility factors, may have especially high arsenic-related cancer risks. This type of new information could be useful in designing environmental regulations and policies that adequately protect for children, fetuses, and other potentially susceptible groups from the carcinogenic effects of arsenic.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Epidemiology of Cancer Study Section (EPIC)
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Dilworth, Caroline H
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University of California Berkeley
Public Health & Prev Medicine
Schools of Public Health
United States
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Nardone, Anthony; Ferreccio, Catterina; Acevedo, Johanna et al. (2017) The impact of BMI on non-malignant respiratory symptoms and lung function in arsenic exposed adults of Northern Chile. Environ Res 158:710-719
de la Rosa, Rosemarie; Steinmaus, Craig; Akers, Nicholas K et al. (2017) Associations between arsenic (+3 oxidation state) methyltransferase (AS3MT) and N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) polymorphisms, arsenic metabolism, and cancer risk in a chilean population. Environ Mol Mutagen 58:411-422
Hall, Emily M; Acevedo, Johanna; López, Francisca González et al. (2017) Hypertension among adults exposed to drinking water arsenic in Northern Chile. Environ Res 153:99-105
Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna et al. (2016) High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile. Toxicol Appl Pharmacol 313:10-15
Steinmaus, Craig; Castriota, Felicia; Ferreccio, Catterina et al. (2015) Obesity and excess weight in early adulthood and high risks of arsenic-related cancer in later life. Environ Res 142:594-601
Steinmaus, Craig; Ferreccio, Catterina; Smith, Allan H (2015) Three Authors Reply. Am J Epidemiol 182:90-2
Steinmaus, Craig; Ferreccio, Catterina; Yuan, Yan et al. (2014) Elevated lung cancer in younger adults and low concentrations of arsenic in water. Am J Epidemiol 180:1082-7
Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna et al. (2014) Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure. Cancer Epidemiol Biomarkers Prev 23:1529-38
Melak, Dawit; Ferreccio, Catterina; Kalman, David et al. (2014) Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile. Toxicol Appl Pharmacol 274:225-31
Ferreccio, Catterina; Smith, Allan H; Durán, Viviana et al. (2013) Case-control study of arsenic in drinking water and kidney cancer in uniquely exposed Northern Chile. Am J Epidemiol 178:813-8

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