State of the science on outdoor air pollution exposure and liver cancer risk.

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 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.