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Title: Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

Abstract

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., < 200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend < 0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend < 0.001). In analyses confined to subjects only with arsenic water concentrations < 200 μg/L (median = 60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared tomore » subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. - Highlights: • Urine arsenic metabolites were measured in cancer cases and controls from Chile. • Higher urine %MMA values were associated with increased lung and bladder cancer. • %MMA-cancer associations were seen at drinking water arsenic levels < 200 μg/L.« less

Authors:
 [1];  [2];  [3];  [4]; ; ;  [2]; ; ;  [5];  [5]
  1. Global Health Sciences, University of California, San Francisco, San Francisco, CA (United States)
  2. Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile)
  3. School of Public Health and Community Medicine, University of Washington, Seattle, WA (United States)
  4. Hospital Regional de Antofagasta, Antofagasta (Chile)
  5. Arsenic Health Effects Research Group, School of Public Health, University of California, Berkeley, Berkeley, CA (United States)
Publication Date:
OSTI Identifier:
22285574
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 274; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARSENIC; BLADDER; CHILE; CONCENTRATION RATIO; DRINKING WATER; IN VITRO; LUNGS; METABOLISM; METABOLITES; METHYLATION; NEOPLASMS; TOXICITY

Citation Formats

Melak, Dawit, Ferreccio, Catterina, Kalman, David, Parra, Roxana, Acevedo, Johanna, Pérez, Liliana, Cortés, Sandra, Smith, Allan H., Yuan, Yan, Liaw, Jane, Steinmaus, Craig, and Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA. Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile. United States: N. p., 2014. Web. doi:10.1016/J.TAAP.2013.11.014.
Melak, Dawit, Ferreccio, Catterina, Kalman, David, Parra, Roxana, Acevedo, Johanna, Pérez, Liliana, Cortés, Sandra, Smith, Allan H., Yuan, Yan, Liaw, Jane, Steinmaus, Craig, & Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA. Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile. United States. https://doi.org/10.1016/J.TAAP.2013.11.014
Melak, Dawit, Ferreccio, Catterina, Kalman, David, Parra, Roxana, Acevedo, Johanna, Pérez, Liliana, Cortés, Sandra, Smith, Allan H., Yuan, Yan, Liaw, Jane, Steinmaus, Craig, and Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA. 2014. "Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile". United States. https://doi.org/10.1016/J.TAAP.2013.11.014.
@article{osti_22285574,
title = {Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile},
author = {Melak, Dawit and Ferreccio, Catterina and Kalman, David and Parra, Roxana and Acevedo, Johanna and Pérez, Liliana and Cortés, Sandra and Smith, Allan H. and Yuan, Yan and Liaw, Jane and Steinmaus, Craig and Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA},
abstractNote = {In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., < 200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend < 0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend < 0.001). In analyses confined to subjects only with arsenic water concentrations < 200 μg/L (median = 60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. - Highlights: • Urine arsenic metabolites were measured in cancer cases and controls from Chile. • Higher urine %MMA values were associated with increased lung and bladder cancer. • %MMA-cancer associations were seen at drinking water arsenic levels < 200 μg/L.},
doi = {10.1016/J.TAAP.2013.11.014},
url = {https://www.osti.gov/biblio/22285574}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 274,
place = {United States},
year = {Wed Jan 15 00:00:00 EST 2014},
month = {Wed Jan 15 00:00:00 EST 2014}
}