Increased Mortality from Lung Cancer and Bronchiectasis in Young Adults
Increased Mortality from Lung Cancer and Bronchiectasis in Young Adults
Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta is the second largest city in Chile and had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. This unique exposure scenario provides a rare opportunity to investigate the long-term mortality impact of early-life arsenic exposure. In this study, we compared mortality rates in Antofagasta in the period 19892000 with those of the rest of Chile, focusing on subjects who were born during or just before the peak exposure period and who were 3049 years of age at the time of death. For the birth cohort born just before the high-exposure period (19501957) and exposed in early childhood, the standardized mortality ratio (SMR) for lung cancer was 7.0 [95% confidence interval (CI) , 5.48.9 ; p < 0.001] and the SMR for bronchiectasis was 12.4 (95% CI, 3.331.7 ; p < 0.001) . For those born during the high-exposure period (19581970) with probable exposure in utero and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.59.9 ; p < 0.001) for lung cancer and 46.2 (95% CI, 21.187.7 ; p < 0.001) for bronchiectasis. These findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease.
The International Agency for Research on Cancer (IARC) has classified arsenic in drinking water as a group 1 carcinogen that causes skin cancer, bladder cancer, and lung cancer (IARC 2002). Substantial evidence supports the biologic plausibility that exposure to arsenic can lead to skin and bladder cancer. For example, arsenic concentrates in the skin and is known to cause nonmalignant skin lesions [National Research Council (NRC) 2001], and the major pathway of excretion is in urine, giving plausibility to increased bladder cancer rates (NRC 2001). Although it is known that inhalation of arsenic may cause lung cancer, the findings of increased lung cancer mortality after ingestion in drinking water were unexpected because all other known lung carcinogens act via inhalation. However, the evidence based on multiple studies in Taiwan (Chen and Wang 1990; Chen et al. 1985, 1988; Wu et al. 1989), Chile (Ferreccio et al. 2000; Smith et al. 1998), Argentina (Hopenhayn-Rich et al. 1998), and Japan (Tsuda et al. 1989, 1995) is sufficient to conclude that there is a causal relationship. In fact, lung cancer is the main long-term cause of death from ingesting arsenic in drinking water (NRC 2001). In region II of Chile, which includes the city of Antofagasta, overall lung cancer mortality rates for men and women were previously found to be at least 3-fold higher than for the rest of Chile (Smith et al. 1998), and lung cancer relative risk estimates increased nearly 9-fold in those with the highest exposures (Ferreccio et al. 2000).
Several known lung carcinogens cause chronic nonmalignant respiratory diseases, including cigarette smoking, which causes chronic obstructive pulmonary disease (COPD); asbestos, which causes asbestosis; and silica, which causes silicosis. To date, however, relatively little attention has been given to whether or not ingestion of arsenic in drinking water causes nonmalignant pulmonary disease. The first reports of chronic respiratory symptoms came from small investigations in Antofagasta in the 1970s (Zaldivar 1974, 1977, 1980; Zaldivar and Ghai 1980). Before 1958, the water supply in the main city of Antofagasta had an arsenic concentration of about 90 µg/L. A growing population led to supplementation of Antofagasta's water supply in the late 1950s with water from rivers with arsenic concentrations near 1,000 µg/L. Because this area is among the driest places on Earth, there are very few individual water supplies, and almost everyone drinks water from the same municipal sources. After the installation of a new treatment plant in 1971, arsenic levels in Antofagasta water dropped abruptly to about 90 µg/L and have been progressively reduced further in recent years (Ferreccio et al. 2000). These data are shown in Figure 1.
(Enlarge Image)
Figure 1.
Arsenic concentrations in Antofagasta/Mejillones water by year. An arsenic removal plant was installed in 1971.
In a 1998 publication concerning region II, increased COPD mortality was reported for the 30- to 39-year age group (Smith et al. 1998). Based on the time period in which mortality was assessed (19891993), subjects in the 30- to 39-year age group would have been in utero or young children at the time of the peak exposure period in Antofagasta. These results were based on a small number of cases but were later supported by findings from other arsenic-exposed regions. For example, increases in symptoms of chronic respiratory disease were found to be associated with arsenic ingestion in studies in West Bengal, India (De et al. 2004; Guha Mazumder et al. 2000) and Bangladesh (Milton and Rahman 2002). Recently, two studies in West Bengal involving participants with arsenic-caused skin lesions reported major deficits in pulmonary function (von Ehrenstein et al. 2005) and a 10-fold increase in prevalence of bronchiectasis identified by high-resolution computed tomography (Guha Mazumder et al. 2005).
The distinct period of high arsenic exposure in Antofagasta from 1958 through 1970 offers the opportunity to investigate the health effects of early-life arsenic exposure. In this study, we take advantage of this unique situation in order to assess adult mortality in those born during the high-exposure period who would have experienced exposure in utero as well as early childhood, and those born just before 1958 who would have experienced high exposure during childhood but not in utero.
Abstract and Introduction
Abstract
Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta is the second largest city in Chile and had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. This unique exposure scenario provides a rare opportunity to investigate the long-term mortality impact of early-life arsenic exposure. In this study, we compared mortality rates in Antofagasta in the period 19892000 with those of the rest of Chile, focusing on subjects who were born during or just before the peak exposure period and who were 3049 years of age at the time of death. For the birth cohort born just before the high-exposure period (19501957) and exposed in early childhood, the standardized mortality ratio (SMR) for lung cancer was 7.0 [95% confidence interval (CI) , 5.48.9 ; p < 0.001] and the SMR for bronchiectasis was 12.4 (95% CI, 3.331.7 ; p < 0.001) . For those born during the high-exposure period (19581970) with probable exposure in utero and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.59.9 ; p < 0.001) for lung cancer and 46.2 (95% CI, 21.187.7 ; p < 0.001) for bronchiectasis. These findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease.
Introduction
The International Agency for Research on Cancer (IARC) has classified arsenic in drinking water as a group 1 carcinogen that causes skin cancer, bladder cancer, and lung cancer (IARC 2002). Substantial evidence supports the biologic plausibility that exposure to arsenic can lead to skin and bladder cancer. For example, arsenic concentrates in the skin and is known to cause nonmalignant skin lesions [National Research Council (NRC) 2001], and the major pathway of excretion is in urine, giving plausibility to increased bladder cancer rates (NRC 2001). Although it is known that inhalation of arsenic may cause lung cancer, the findings of increased lung cancer mortality after ingestion in drinking water were unexpected because all other known lung carcinogens act via inhalation. However, the evidence based on multiple studies in Taiwan (Chen and Wang 1990; Chen et al. 1985, 1988; Wu et al. 1989), Chile (Ferreccio et al. 2000; Smith et al. 1998), Argentina (Hopenhayn-Rich et al. 1998), and Japan (Tsuda et al. 1989, 1995) is sufficient to conclude that there is a causal relationship. In fact, lung cancer is the main long-term cause of death from ingesting arsenic in drinking water (NRC 2001). In region II of Chile, which includes the city of Antofagasta, overall lung cancer mortality rates for men and women were previously found to be at least 3-fold higher than for the rest of Chile (Smith et al. 1998), and lung cancer relative risk estimates increased nearly 9-fold in those with the highest exposures (Ferreccio et al. 2000).
Several known lung carcinogens cause chronic nonmalignant respiratory diseases, including cigarette smoking, which causes chronic obstructive pulmonary disease (COPD); asbestos, which causes asbestosis; and silica, which causes silicosis. To date, however, relatively little attention has been given to whether or not ingestion of arsenic in drinking water causes nonmalignant pulmonary disease. The first reports of chronic respiratory symptoms came from small investigations in Antofagasta in the 1970s (Zaldivar 1974, 1977, 1980; Zaldivar and Ghai 1980). Before 1958, the water supply in the main city of Antofagasta had an arsenic concentration of about 90 µg/L. A growing population led to supplementation of Antofagasta's water supply in the late 1950s with water from rivers with arsenic concentrations near 1,000 µg/L. Because this area is among the driest places on Earth, there are very few individual water supplies, and almost everyone drinks water from the same municipal sources. After the installation of a new treatment plant in 1971, arsenic levels in Antofagasta water dropped abruptly to about 90 µg/L and have been progressively reduced further in recent years (Ferreccio et al. 2000). These data are shown in Figure 1.
(Enlarge Image)
Figure 1.
Arsenic concentrations in Antofagasta/Mejillones water by year. An arsenic removal plant was installed in 1971.
In a 1998 publication concerning region II, increased COPD mortality was reported for the 30- to 39-year age group (Smith et al. 1998). Based on the time period in which mortality was assessed (19891993), subjects in the 30- to 39-year age group would have been in utero or young children at the time of the peak exposure period in Antofagasta. These results were based on a small number of cases but were later supported by findings from other arsenic-exposed regions. For example, increases in symptoms of chronic respiratory disease were found to be associated with arsenic ingestion in studies in West Bengal, India (De et al. 2004; Guha Mazumder et al. 2000) and Bangladesh (Milton and Rahman 2002). Recently, two studies in West Bengal involving participants with arsenic-caused skin lesions reported major deficits in pulmonary function (von Ehrenstein et al. 2005) and a 10-fold increase in prevalence of bronchiectasis identified by high-resolution computed tomography (Guha Mazumder et al. 2005).
The distinct period of high arsenic exposure in Antofagasta from 1958 through 1970 offers the opportunity to investigate the health effects of early-life arsenic exposure. In this study, we take advantage of this unique situation in order to assess adult mortality in those born during the high-exposure period who would have experienced exposure in utero as well as early childhood, and those born just before 1958 who would have experienced high exposure during childhood but not in utero.
