Supplementary Material for: Exposure to Air Pollution and Survival in follow-up After Hepatocellular Carcinoma

Introduction: Air pollutants are classified as carcinogens by the International Agency for Research on Cancer. Long-term exposure to ambient particulate matter with an aerodiameter of 2.5 µm or lower (PM2.5) has been reported to be linked with increased mortality due to hepatocellular carcinoma (HCC). However, the effects of air pollutants other than PM2.5 on HCC-related mortality have not been fully investigated. Accordingly, we conducted this study to assess the effect of long-term exposure to air pollutants (PM2.5 and nitrogen dioxide [NO2]) on HCC-related mortality. Method: In 2005, the Taiwan Liver Cancer Network (TLCN) was established by the National Research Program for Genomic Medicine to recruit liver cancer patients from 5 major medical centers in northern, central, and southern Taiwan. The TLCN had successfully recruited 9,344 patients by the end of 2018. In this study, we included 1,000 patients randomly sampled from the TLCN to assess the effect of exposure to air pollutants on HCC mortality after HCC diagnosis. Daily averages of PM2.5 and NO2 concentrations were retrieved from 77 air quality monitoring stations and interpolated to the townships of patients’ residence by using the Kriging method. The effect of air pollutants on HCC survival was assessed using a Cox proportional hazards model. Results: A total of 940 patients were included in the analysis. After adjusting for potential confounders and mutually adjusting for co-pollutants, we observed that the hazards ratio (95% confidence interval) for HCC-related mortality for every 1 μg/m3 increase in PM2.5 concentration was 1.11 (1.08-1.14), and that for every 1-ppb increase in NO2 concentration was 1.08 (1.03- 1.13). Conclusion: Our study suggests that long-term exposure to PM2.5 and NO2 was associated with decreased survival time in patients with HCC in Taiwan.