Abstract
BACKGROUND: There is emerging evidence that air pollution exposure increases the risk of developing liver cancer. To date, there have been four epidemiologic studies conducted in the United States, Taiwan, and Europe showing generally consistent positive associations between ambient exposure to air pollutants, including particulate matter <2.5 μm in aerodynamic diameter (PM(2.5)) and nitrogen dioxide (NO(2)), and liver cancer risk. There are several research gaps and thus valuable opportunities for future work to continue building on this expanding body of literature. The objectives of this paper are to narratively synthesize existing epidemiologic literature on the association between air pollution exposure and liver cancer incidence and describe future research directions to advance the science of understanding the role of air pollution exposure in liver cancer development. FUTURE RESEARCH DIRECTIONS: include 1) accounting for potential confounding by established risk factors for the predominant histological subtype, hepatocellular carcinoma (HCC); 2) examination of incident primary liver cancer outcomes with consideration of potential differential associations according to histology; 3) air pollution exposure assessments considering early-life and/or historical exposures, residential histories, residual confounding from other sources of air pollution (e.g., tobacco smoking), and integration of geospatial ambient exposure modeling with novel biomarker technologies; 4) examination of air pollution mixtures experienced in the exposome; 5) consideration of increased opportunities for exposure to outdoor air pollution due to climate change (e.g., wildfires); and 6) consideration of modifying factors for air pollution exposure, such as socioeconomic status, that may contribute to disparities in liver cancer incidence. CONCLUSIONS: In light of mounting evidence demonstrating that higher levels of air pollution exposure increase the risk for developing liver cancer, methodological considerations primarily concerning residual confounding and improved exposure assessment are warranted to robustly demonstrate an independent association for air pollution as a hepatocarcinogen.