Exposure to PM_2.5 Metal Constituents and Liver Cancer Risk in REVEAL-HBV

Background: Ambient particulate matter is classified as a human Class 1 carcinogen, and recent studies found a positive relationship between fine particulate matter (PM_2.5) and liver cancer. Nevertheless, little is known about which specific metal constituent contributes to the development of liver cancer. Objective: To evaluate the association of long-term exposure to metal constituents in PM_2.5 with the risk of liver cancer using a Taiwanese cohort study. Methods: A total of 13,511 Taiwanese participants were recruited from the REVEAL-HBV in 1991–1992. Participants’ long-term exposure to eight metal constituents (Ba, Cu, Mn, Sb, Zn, Pb, Ni, and Cd) in PM_2.5 was based on ambient measurement in 2002–2006 followed by a land-use regression model for spatial interpolation. We ascertained newly developed liver cancer (ie, hepatocellular carcinoma [HCC]) through data linkage with the Taiwan Cancer Registry and national health death certification in 1991–2014. A Cox proportional hazards model was utilized to assess the association between exposure to PM_2.5 metal component and HCC. Results: We identified 322 newly developed HCC with a median follow-up of 23.1 years. Long-term exposure to PM_2.5 Cu was positively associated with a risk of liver cancer. The adjusted hazard ratio (HR) was 1.13 (95% confidence interval [CI], 1.02–1.25; P = 0.023) with one unit increment on Cu normalized by PM_2.5 mass concentration in the logarithmic scale. The PM_2.5 Cu-HCC association remained statistically significant with adjustment for co-exposures to other metal constituents in PM_2.5 . Conclusion: Our findings suggest PM_2.5 containing Cu may attribute to the association of PM_2.5 exposure with liver cancer.