Liu and Wu WHO region/country Africa Democratic Republic of Congo Ethiopia The Gambia Kenya Mozambique Nigeria South Africa Tanzania Zimbabwe Total region North America Canada United States Total region Latin America Argentina Brazil Mexico Total region Eastern Mediterranean Egypt Iran Pakistan Sudan Total region Southeast Asia India Indonesia Thailand Total region Western Pacific region Australia China Korea Malaysia Philippines Total region Europe Eastern Europe Southern Europe Western Europe Total region Total (world) Total annual HCC cases attributable to aflatoxin worldwide aData from Central Intelligence Agency 2009. Western Paciﬁc 20% Southeast Asia 27% 1.7 68 85 38 21 149 48 41 13 755 33 300 333 40 190 109 562 81 66 172 41 569 1,150 237 63 ~1,734 21 1,300 50 28 90 ~1,740 290 144 183 617 6,280 1–173 11–288 1–17 11–450 73–361 0–79 1–195 19–50 1 8 9 1,800–2,940 2,150–9,300 0–16 4–930 152–924 589–2,980 51–452 33–56 116–832 58–717 446–3,720 438–11,200 203–2,820 307–439 1,740–17,300 0–1 1,990–4,430 5–29 40–372 333–462 2,710–6,510 94–114 0–56 5–24 99–184 7,700–40,000 25,200–155,000 1–551 21–643 3–117 44–2,270 111–1,200 8,200–13,400 0–255 1–554 68–249 9,230–50,600 1 1–5 2–5 0–5 3–969 14–83 84–2,060 37–1400 4–9 119–851 140–5,950 341–13,200 331–16,200 160–4,340 461–1,100 1,460–27,600 0–1 5,300–14,400 6–45 63–588 594–2,330 6,310–21,200 61–244 0–121 1–7 62–372 17,500–115,000 Europe 0% Africa 40% North America 0% Latin America 3% Eastern Mediterranean 10% Table 4. Estimated annual global burden of HCC cases attributable to aflatoxin exposure in HBsAg- positive and HBsAg-negative populations. Population (millions)a Annual HCC cases HBsAg-negative HBsAg-positive Figure 1. Distribution of HCC cases attributable to aflatoxin in different regions of the world. 822 ovlume 118 | number 6 | June 2010 • Environmental Health Perspectives obviously moldy maize and groundnuts. But in drought seasons, oftentimes people have no choice but to eat moldy food or starve (Williams 2008). Multiple public health interventions exist to control the burden of aflatoxin in the body and to prevent HCC. These inter- ventions, described in greater detail in Wu and Khlangwiset (2010), can be grouped into three categories: agricultural, dietary, and clinical. Agricultural interventions can be applied either in the field (preharvest) or in storage and transportation (postharvest) to reduce aflatoxin levels in key crops. They can thus be considered primary interventions. Dietary and clinical interventions can be con- sidered secondary interventions. They cannot reduce actual aflatoxin levels in food, but they can reduce aflatoxin-related illness, either by reducing aflatoxin’s bioavailability in the body or by ameliorating aflatoxin-induced damage. Because aflatoxin-mediated mutations may precede HCC by several years, the effects of reducing aflatoxin exposure on HCC inci- dence may take time to become apparent (Szymañska et al. 2009). One highly effective clinical interven- tion to reduce aflatoxin-related HCC is vac- cination against HBV. Vaccinating children against HBV has, over the past 30 years, sig- nificantly decreased HBV infection in sev- eral regions, including Europe (Bonanni et al. 2003; Williams et al. 1996), Taiwan (Chen et al. 1996), and Thailand (Jutavijittum et al. 2005). This vaccine will, over time, lessen the global carcinogenic impact of aflatoxin, because removing the synergistic impact between HBV and aflatoxin expo- sure would significantly reduce HCC risk. However, there are currently roughly 360 million chronic HBV carriers worldwide, and HBV vaccination is still not incorporated into many national immunization programs (Wild and Hall 2000). Thus, adopting measures to reduce dietary exposure to aflatoxins is crucial for public health. Our study highlights the significant role of aflatoxin in contributing to global liver cancer burden. Most cases occur in sub- Saharan Africa, Southeast Asia, and China, where populations suffer from both high HBV prevalence and largely uncontrolled exposure to aflatoxin in the food. Not all risk factors for HCC, including synergistic roles between aflatoxin and other carcinogens, are clearly understood; hence, these estimates for number of global aflatoxin-induced HCC cases have a large range. Although it is impos- sible to completely eliminate aflatoxin in food worldwide, it is possible to significantly reduce levels and dramatically reduce liver cancer incidence worldwide. The challenge remains to deliver these interventions to places of the world where they are most needed.