Global Burden of Aflatoxin-induced Hepatocellular Carcinoma: A Risk Assessment

Yan Liu; Felicia Wu

Environ Health Perspect. 2010;118(6):818-824.

Results

Table 1 lists the prevalence of chronic HBV infection by world region, as measured by HBsAg in different parts of the world. Although these different estimates involve uncertainty and variability, all data are from literature published in or after 2000, to ensure that the HBV prevalence estimates are as current and as relevant as possible. Countries are grouped by WHO designated regions (WHO 2005): Africa, North America and Latin America, Eastern Mediterranean, Southeast Asia, Western Pacific, and Europe. Some regions were divided into subgroups because of significantly varied aflatoxin exposure and HBV prevalence within the region.

Table 2 provides calculations of maize and peanut consumption in select countries of the world. The GEMS/Food Consumption Cluster Diets database divides countries of the world into 13 groups based on diets. For each group cluster, the GEMS food consumption database has estimated the amount of cereals, nuts, and oilseeds consumed. We thus estimated average maize and nut consumption by individual country. There are limitations to these data because of the clustering into 13 groups (with potentially wide ranges among nations within a group), as well as variability in data quality regarding diet and aflatoxin exposure estimates.

We estimated (based on Tables 1 and 2) or found in the literature the average aflatoxin exposure in different world regions and then calculated the estimated incidence of aflatoxin-induced HCC, with and without the synergistic impact with HBV, in the corresponding populations of each nation and world region (Table 3). Within each WHO-designated region, we found aflatoxin exposures in the most populous nations. The "in general" rows in Table 3 represent a small proportion of each region: nations in which aflatoxin data were not available, or very small nations. For these, we assumed a range for aflatoxin exposure that incorporated the ranges of the nations within the region for which we found aflatoxin data.

These data provide the necessary information to calculate the total estimated cases of aflatoxin-induced HCC cases annually, worldwide. Table 4 lists populations for each relevant nation and world region. Accounting for chronic HBV infection prevalence as shown in Table 1, and the risk estimates for HBV-positive versus HBV-negative individuals in Table 3, the numbers of cases of aflatoxin-induced HCC can be estimated in each world region. These are then summed to produce a global estimate of the number of annual aflatoxin-induced HCC cases. Our estimate is that anywhere from 25,200 to 155,000 annual HCC cases worldwide may be attributable to aflatoxin exposure.

Figure 1 illustrates the distribution of HCC cases attributable to aflatoxin globally. The categories denote WHO world regions. Sub-Saharan Africa is the most important region for HCC cases attributable to aflatoxin; Southeast Asia and China (in the Western Pacific region) are also key regions where aflatoxin-related HCC is an important risk. Relatively fewer cases occur in the Americas, Eastern Mediterranean, and Europe. Although Australia and New Zealand are grouped with the Western Pacific region, these nations also have low aflatoxin-induced HCC incidence. It is notable that in Mexico, where HBV prevalence is relatively low but aflatoxin contamination in food is relatively high, aflatoxin appears to be a significant risk factor for HCC among those without HBV (an estimated 152–924 HCC cases per year per 100,000 people).

(Enlarge Image)

Figure 1.

Distribution of HCC cases attributable to aflatoxin in different regions of the world.

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Cite this: Global Burden of Aflatoxin-induced Hepatocellular Carcinoma: A Risk Assessment - Medscape - Jun 01, 2010.

Table 1. Estimates of HBV prevalence in select countries based on HBsAg seroprevalence.
WHO region/country	References	Chronic HBV prevalence (%)
Africa
Democratic Republic of Congo	Batina et al. 2007; Mbendi et al. 2001	6–10
Ethiopia	Abebe et al. 2003; Shimelis et al. 2008	6–7
The Gambia	Kirk et al. 2004; Vall et al. 1990	15–20
Kenya	Kiire 1996; Tuei 1994	11–15
Mozambique	Cunha et al. 2007	4.5–10.6
Nigeria	Fasola et al. 2008	13.2
South Africa	Custer et al. 2004; Kiire 1996	3.3–10.4
Tanzania	Hasegawa et al. 2006; Matee et al. 2006; Miller et al. 1998	5–9
Zimbabwe	Kiire 1996; Tswana et al. 1996	10–15
Others	Kiire 1996; Matee et al. 2006; Tayou et al. 2009	9–20
North America and Latin America
Canada	Minuk and Uhanova 2001; Zhang et al. 2001	1–2
United States	CDC 2009; Cohen et al. 2008; WHO 2005	0.3–2
Argentina	Paraná and Almeida 2005; Torres 1996	0.8–1.1
Brazil	Paraná and Almeida 2005; Torres 1996	2.1–3.4
Mexico	Roman et al. 2009	< 0.3
Others	Paraná and Almeida 2005; Torres 1996	0.5–3
Eastern Mediterranean
Egypt	Ismail et al. 2009; Lehman and Wilson 2009; Youssef et al. 2009	2.2–10.1
Iran	Kafi-Abad et al. 2009a, 2009b	0.41–0.56
Pakistan	Butt and Amin 2008; Khattak et al. 2002	3.3
Sudan	Elsheikh et al. 2007	6–26
Others	Abou et al. 2009; Batayneh and Bdour 2002; Ameen et al. 2005; WHO 2005	0.65–10
Southeast Asia
India	Behal et al. 2008; Tandon et al. 1996	2.4– 4.7
Indonesia	Hong et al. 2001; Merican et al. 2000; van Hattum et al. 2003	2.5–5
Thailand	Tanprasert and Somjitta 1993	4.6–8
Others	Alam et al. 2007; Ali et al. 2009; Jafri et al. 2006; WHO 2005	2–7
Western Pacific
Australia	WHO 2007	< 1
China	Merican et al. 2000; WHO 2007	8–10
Malaysia	Merican et al. 2000; WHO 2007	5
Philippines	Domingo 1997; Lansang 1996; WHO 2007	5–16
Korea	Song et al. 2009; WHO 2007	4–5
Others	Gust 1996; Merican et al. 2000; Nakata et al. 1994	1–10
Europe
Eastern Europe	Magdzik 2000; Resuli et al. 2009	2–7
Southern Europe	Da Villa 1998; Gogos et al. 2003; WHO 2005	2–7
Western Europe	Hahné et al. 2004; WHO 2005; Jilg et al. 2001	0.5–1

CDC, Centers for Disease Control and Prevention.

Table 2. Maize and peanut consumption in select countries.
WHO region/country	Maize^a(g/person/day)	Peanut^b(g/person/day)
Africa
Democratic Republic of Congo	57	52
Ethiopia	83	13
The Gambia	57	52
Kenya	248	11
Mozambique	248	11
Nigeria	57	52
South Africa	248	11
Tanzania	248	11
Zimbabwe	248	11
North America and Latin America
Canada	86	17
United States	86	17
Argentina	86	17
Brazil	63	2
Mexico	300	5
Eastern Mediterranean
Egypt	136	5
Iran	32	2
Pakistan	35	18
Sudan	57	52
Southeast Asia
India	35	18
Indonesia	35	18
Thailand	35	18
Western Pacific
Australia	86	17
China	35	18
Malaysia	35	18
Philippines	59	2
Republic of Korea	59	2
Europe
Eastern Europe	32	2–10
Southern Europe	148	7
Western Europe	33	10

Data are adapted from GEMS/Food Consumption Cluster Diets database (WHO 2006).
^aIncluding maize, flour and germ. ^bIncluding groundnuts in shell and shelled

Table 3. Estimated HCC incidence attributable to aflatoxin, by WHO region.
WHO region/country	Reference	Aflatoxin exposure(ng/kg body weight/day^a)	Estimated annual HCC (per 100,000)
WHO region/country	Reference	Aflatoxin exposure(ng/kg body weight/day^a)	HBsAg-negative	HBsAg-positive
Africa
Democratic Republic of Congo	Manjula et al. 2009^b	0.07–27	0.0007–0.27	0.02–8.10
Ethiopia	Ayalew et al. 2006^b	1.4–36	0.01–0.36	0.42–10.8
The Gambia	Hall and Wild 1994; Shephard 2008	4–115	0.04–1.15	1.20–34.5
Kenya	Hall and Wild 1994; Shephard 2008	3.5–133	0.04–1.33	1.05–39.9
Mozambique	Hall and Wild 1994	39–180	0.39–1.80	11.7–54.0
Nigeria	Bandyopadhyay et al. 2007; Bankole and Mabekoje 2004^b	139–227	1.39–2.27	41.7–68.1
South Africa	Hall and Wild 1994; Shephard 2003	0–17	0–0.17	0–5.10
Tanzania	Manjula et al. 2009^b	0.02–50	0.0002–0.50	0.06–15.0
Zimbabwe	IPCS/WHO 1998	17.5–42.5	0.18–0.43	5.25–12.8
In general^c	Hall and Wild 1994; Shephard 2008	10–180	0.10–1.80	3.0–54.0
North America
Canada	Kuiper-Goodman 1995	0.2–0.4^d	0.002–0.004	0.06–0.12
United States	IPCS/WHO 1998	0.26	0.003	0.08
In general^c		0.26–1	0.003–0.01	0.08–0.3
Latin America
Argentina	Etcheverry et al. 1999; Solovey et al. 1999^b	0–4	0–0.04	0–1.20
Brazil	IARC 2002; Midio et al. 2001; Oliveira et al. 2009; Vargas et al. 2001^b	0.23–50	0.002–0.50	0.07–15.0
Mexico	García and Heredia 2006; Guzmán-de-Peña and Peña-Cabriales 2005; Torres et al. 1995^b	14–85	0.14–0.85	4.20–25.5
In general^c		20–50	0.20–0.50	6.0–15.0
Eastern Mediterranean
Egypt	Anwar et al. 2008^b	7–57	0.07–0.57	2.1–17.1
Iran	Hadiani et al. 2009; Mazaheri 2009^b	5–8.5	0.05–0.09	1.50–2.55
Pakistan	Munir et al. 1989^b	7–50	0.07–0.50	2.10–15.0
Sudan	Omer et al. 1998	19–186	0.19–1.86	5.70–55.8
In general^c		10–80	0.10–0.80	3.00–24.0
Southeast Asia
India	Vasanthi 1998	4–100	0.04–1.00	1.20–30.0
Indonesia	Ali et al. 1998; IARC 2002; Noviandi et al. 2001^b	9–122	0.09–1.22	2.7–36.6
Thailand	Hall and Wild 1994; Lipigorngoson et al. 2003^b	53–73	0.53–0.73	15.9–21.9
In general^c		30–100	0.30–1.00	9.00–30.0
Western Pacific
Australia	NHMRC 1992; Pitt and Tomaska 2001	0.15–0.18	~0.002	~0.05
China	Li et al. 2001; Qian et al. 1994; Wang and Liu 2007; Wang et al. 2001^b	17–37	0.17–0.37	5.10–11.1
Malaysia	Ali et al. 1999; IARC 2002^b	15–140	0.15–1.4	4.5–42
Philippines	Ali et al. 1999; IARC 2002; Sales and Yoshizawa 2005^b	44–54	0.44–0.54	13.2–16.2
Republic of Korea	Ok et al. 2007; Park et al. 2004	1.2–6	0.01–0.06	0.36–1.80
In general^c		15–50 (except Australia and New Zealand)	0.15–0.50	4.5–15.0
Europe
Eastern Europe	Malir et al. 2006^e	3.5–4	0.04	~1.20
Southern Europe	Battilani et al. 2008; Giray et al. 2007^f	0–4	0–0.04	0–1.20
Western Europe	IARC 2002	0.3–1.3	0.003–0.01	0.09–0.39
In general^c		0–4	0–0.04	0–1.2

NHMRC, National Health and Medical Research Council. ^aAssuming 60 kg body weight per individual. ^bAflatoxin exposure was estimated by multiplying aflatoxin concentrations in staple foods by consumption rates of those foods (WHO 2006). ^cAflatoxin exposure estimates and consequent HCC cases for all other countries classified in the same WHO region. ^dAflatoxin exposure of 1–2 ng/kg body weight/day was measured in children's diets; here we assume the adult daily aflatoxin intake is 20% that of children. ^eAverage daily aflatoxin intake was estimated based on AFB1 contamination levels in Czech maize, multiplied by average daily maize consumption in Eastern Europe. ^fAverage daily aflatoxin intake was estimated based on AFB1 contamination levels in maize of North Italy and Turkey, multiplied by average daily maize consumption in Southern Europe.

Table 4. Estimated annual global burden of HCC cases attributable to aflatoxin exposure in HBsAg-positive and HBsAg-negative populations.
WHO region/country	Population (millions)^a	Annual HCC cases
WHO region/country	Population (millions)^a	HBsAg-negative	HBsAg-positive
Africa
Democratic Republic of Congo	68	1–173	1–551
Ethiopia	85	11–288	21–643
The Gambia	1.7	1–17	3–117
Kenya	38	11–450	44–2,270
Mozambique	21	73–361	111–1,200
Nigeria	149	1,800–2,940	8,200–13,400
South Africa	48	0–79	0–255
Tanzania	41	1–195	1–554
Zimbabwe	13	19–50	68–249
Total region	755	2,150–9,300	9,230–50,600
North America
Canada	33	1	1
United States	300	8	1–5
Total region	333	9	2–5
Latin America
Argentina	40	0–16	0–5
Brazil	190	4–930	3–969
Mexico	109	152–924	14–83
Total region	562	589–2,980	84–2,060
Eastern Mediterranean
Egypt	81	51–452	37–1400
Iran	66	33–56	4–9
Pakistan	172	116–832	119–851
Sudan	41	58–717	140–5,950
Total region	569	446–3,720	341–13,200
Southeast Asia
India	1,150	438–11,200	331–16,200
Indonesia	237	203–2,820	160–4,340
Thailand	63	307–439	461–1,100
Total region	~1,734	1,740–17,300	1,460–27,600
Western Pacific region
Australia	21	0–1	0–1
China	1,300	1,990–4,430	5,300–14,400
Korea	50	5–29	6–45
Malaysia	28	40–372	63–588
Philippines	90	333–462	594–2,330
Total region	~1,740	2,710–6,510	6,310–21,200
Europe
Eastern Europe	290	94–114	61–244
Southern Europe	144	0–56	0–121
Western Europe	183	5–24	1–7
Total region	617	99–184	62–372
Total (world)	6,280	7,700–40,000	17,500–115,000
Total annual HCC cases attributable to aflatoxin worldwide		25,200–155,000

^aData from Central Intelligence Agency 2009.

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