Estimating the Global Burden of Aflatoxin-Attributable Liver Cancer Risk

Background: Over 4 billion people worldwide are exposed to dietary aflatoxins, which can cause liver cancer (hepatocellular carcinoma, HCC) in humans independently and interact with chronic hepatitis B virus (HBV) infection to increase the cancer risk. However, the global burden of HCC from aflatoxin exposure remains unclear.\ud \ud Objectives: We sought to determine 1) the global burden of HCC attributable to aflatoxin exposure; 2) the population-attributable risk (PAR) of HCC from aflatoxin in high exposure areas; 3) the quantitative model of effects between aflatoxin exposure and HBV infection in increasing liver cancer risk.\ud \ud Methods: We first conducted a quantitative cancer risk assessment, for which we collected global data on foodborne aflatoxin levels, consumption of aflatoxin-contaminated foods, and HBV prevalence. Aflatoxin’s cancer potencies for HBV+ and HBV- individuals, and uncertainty in all variables, were considered in calculating the global burden of aflatoxin-related HCC. Then, we conducted a meta-analysis on the eligible studies identified by literature search. Summary odds ratios (ORs) of aflatoxin-related HCC with 95% confidence intervals were calculated in HBV+ and HBV- individuals, as well as the general population. We calculated the PAR of aflatoxin-related HCC for each study as well as the combined studies, accounting for HBV status.\ud \ud Results: 25,200-155,000 HCC cases worldwide may be attributable to aflatoxin exposure. Most cases occur in sub-Saharan Africa, Southeast Asia, and China, where populations suffer from both high HBV prevalence and largely uncontrolled dietary aflatoxin. In these areas, the PAR of aflatoxin-related HCC with 95% CI was estimated at 17% (14-19%) for overall population, and higher in HBV+ (21%) than HBV- (8.8%) populations. If the one study that contributed most to heterogeneity in the analysis is excluded, the summarized OR of HCC with 95% CI is 73.0 (36.0-148.3) from the combined effects of aflatoxin and HBV, 11.3 (6.75-18.9) from HBV only, and 6.37 (3.74-10.86) from aflatoxin only. The PAR of aflatoxin-related HCC increases to 23% (21-24%). \ud \ud Public Health Significance: Aflatoxin may play a causative role in 4.6-28.2% of all global HCC cases. In high exposure areas, aflatoxin exposure may multiplicatively interact with HBV to induce HCC and attribute to 14-19% of liver cancer cases.\u