Silica Exposure and Lung Cancer Risk
Silica Exposure and Lung Cancer Risk
Crystalline silica has been classified as a human carcinogen by the International Agency for Research on Cancer (Lyon, France); however, few previous studies have provided quantitative data on silica exposure, silicosis, and/or smoking. We investigated a cohort in China (in 1960–2003) of 34,018 workers without exposure to carcinogenic confounders. Cumulative silica exposure was estimated by linking a job-exposure matrix to work history. Cox proportional hazards model was used to conduct exposure-response analysis and risk assessment. During a mean 34.5-year follow-up, 546 lung cancer deaths were identified. Categorical analyses by quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed group. Monotonic exposure-response trends were observed among nonsilicotics (P for trend < 0.001). Analyses using splines showed similar trends. The joint effect of silica and smoking was more than additive and close to multiplicative. For workers exposed from ages 20 to 65 years at 0.1 mg/m of silica exposure, the estimated excess lifetime risk (through age 75 years) was 0.51%. These findings confirm silica as a human carcinogen and suggest that current exposure limits in many countries might be insufficient to protect workers from lung cancer. They also indicate that smoking cessation could help reduce lung cancer risk for silica-exposed individuals.
Crystalline silica is one of the most common minerals and a common particulate air pollutant in both working and living environments. Occupational exposure frequently occurs in a variety of industries, such as metal and coal mining, construction, and clay manufacturing. Recent reports have indicated that more than 1.7 million workers in the United States, more than 2 million in Europe, and more than 23 million in China have been occupationally exposed to crystalline silica dust. In ambient air, crystalline silica can be easily generated from industrial operations, volcanic explosions, and sandstorms. The adverse health effects of silica exposure represent an important global public health concern.
Lung cancer is considered one of the serious consequences of silica exposure. The association has been studied for many decades. In 1997, the International Agency for Research on Cancer (Lyon, France) classified silica as "carcinogenic to humans". However, the working group also stated that the carcinogenicity was not found in all industrial circumstances, and the conclusion remained somewhat controversial because few published studies could provide quantitative exposure-response trends to support causal inference. In 2009, another working group from the International Agency for Research on Cancer focused on exposure-response studies and a pooled analysis of 10 cohort studies and concluded that "crystalline silica in the form of quartz or cristobalite dust causes cancer of the lung". Nonetheless, some critics persist in the view that the weight of evidence from occupational epidemiology does not support a casual association of lung cancer and silica exposure.
The role of silicosis in the development of lung cancer associated with silica exposure remains controversial. Most epidemiologic studies have consistently observed higher risk of lung cancer among silicotics but detected no higher risk or slightly higher risk among nonsilicotics. When silicosis cases are excluded, epidemiologic data from many studies might be insufficient to detect elevated lung cancer risk due to silica exposure. Thus, the carcinogenic role of silica in the absence of silicosis needs further evaluation.
Cigarette smoking is an important potential confounding factor in the evaluation of the carcinogenicity of crystalline silica. However, many studies have not been able to adequately control for its confounding effect because of difficulty collecting detailed smoking data for each participant. Furthermore, the joint effect of smoking and silica exposure remains unclear. Studies with smoking data often have too few lung cancer deaths among never smokers to adequately investigate this issue.
In the late 1980s, a large cohort of 74,040 workers from 29 Chinese metal mines and pottery factories was established in China. Here, we focus on a subcohort of 34,018 workers who were unlikely to have been exposed to other carcinogenic confounders, such as radon, polycyclic aromatic hydrocarbons, and arsenic. We extended prior analyses to 2003 and conducted a quantitative exposure-response analysis and risk assessment for lung cancer, taking into consideration smoking, as well as silicosis. In addition, we investigated the joint effect of silica exposure and smoking in the development of lung cancer.
Abstract and Introduction
Abstract
Crystalline silica has been classified as a human carcinogen by the International Agency for Research on Cancer (Lyon, France); however, few previous studies have provided quantitative data on silica exposure, silicosis, and/or smoking. We investigated a cohort in China (in 1960–2003) of 34,018 workers without exposure to carcinogenic confounders. Cumulative silica exposure was estimated by linking a job-exposure matrix to work history. Cox proportional hazards model was used to conduct exposure-response analysis and risk assessment. During a mean 34.5-year follow-up, 546 lung cancer deaths were identified. Categorical analyses by quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed group. Monotonic exposure-response trends were observed among nonsilicotics (P for trend < 0.001). Analyses using splines showed similar trends. The joint effect of silica and smoking was more than additive and close to multiplicative. For workers exposed from ages 20 to 65 years at 0.1 mg/m of silica exposure, the estimated excess lifetime risk (through age 75 years) was 0.51%. These findings confirm silica as a human carcinogen and suggest that current exposure limits in many countries might be insufficient to protect workers from lung cancer. They also indicate that smoking cessation could help reduce lung cancer risk for silica-exposed individuals.
Introduction
Crystalline silica is one of the most common minerals and a common particulate air pollutant in both working and living environments. Occupational exposure frequently occurs in a variety of industries, such as metal and coal mining, construction, and clay manufacturing. Recent reports have indicated that more than 1.7 million workers in the United States, more than 2 million in Europe, and more than 23 million in China have been occupationally exposed to crystalline silica dust. In ambient air, crystalline silica can be easily generated from industrial operations, volcanic explosions, and sandstorms. The adverse health effects of silica exposure represent an important global public health concern.
Lung cancer is considered one of the serious consequences of silica exposure. The association has been studied for many decades. In 1997, the International Agency for Research on Cancer (Lyon, France) classified silica as "carcinogenic to humans". However, the working group also stated that the carcinogenicity was not found in all industrial circumstances, and the conclusion remained somewhat controversial because few published studies could provide quantitative exposure-response trends to support causal inference. In 2009, another working group from the International Agency for Research on Cancer focused on exposure-response studies and a pooled analysis of 10 cohort studies and concluded that "crystalline silica in the form of quartz or cristobalite dust causes cancer of the lung". Nonetheless, some critics persist in the view that the weight of evidence from occupational epidemiology does not support a casual association of lung cancer and silica exposure.
The role of silicosis in the development of lung cancer associated with silica exposure remains controversial. Most epidemiologic studies have consistently observed higher risk of lung cancer among silicotics but detected no higher risk or slightly higher risk among nonsilicotics. When silicosis cases are excluded, epidemiologic data from many studies might be insufficient to detect elevated lung cancer risk due to silica exposure. Thus, the carcinogenic role of silica in the absence of silicosis needs further evaluation.
Cigarette smoking is an important potential confounding factor in the evaluation of the carcinogenicity of crystalline silica. However, many studies have not been able to adequately control for its confounding effect because of difficulty collecting detailed smoking data for each participant. Furthermore, the joint effect of smoking and silica exposure remains unclear. Studies with smoking data often have too few lung cancer deaths among never smokers to adequately investigate this issue.
In the late 1980s, a large cohort of 74,040 workers from 29 Chinese metal mines and pottery factories was established in China. Here, we focus on a subcohort of 34,018 workers who were unlikely to have been exposed to other carcinogenic confounders, such as radon, polycyclic aromatic hydrocarbons, and arsenic. We extended prior analyses to 2003 and conducted a quantitative exposure-response analysis and risk assessment for lung cancer, taking into consideration smoking, as well as silicosis. In addition, we investigated the joint effect of silica exposure and smoking in the development of lung cancer.
