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Estimating the Global Burden of Aflatoxin-Attributable Liver Cancer Risk

Liu, Yan (2012) Estimating the Global Burden of Aflatoxin-Attributable Liver Cancer Risk. Doctoral Dissertation, University of Pittsburgh.

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    Abstract

    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. 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. 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. 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%). 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.


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    Item Type: University of Pittsburgh ETD
    ETD Committee:
    ETD Committee TypeCommittee MemberEmailORCID
    Committee ChairWu , Feliciafew8@pitt.edu
    Committee MemberBarchowsky, Aaronaab20@pitt.edu
    Committee MemberGoldstein, Bernardbdgold@pitt.edu
    Committee MemberMarsh, Garygmarsh@pitt.edu
    Title: Estimating the Global Burden of Aflatoxin-Attributable Liver Cancer Risk
    Status: Published
    Abstract: 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. 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. 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. 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%). 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.
    Date: 30 January 2012
    Date Type: Completion
    Defense Date: 02 September 2011
    Approval Date: 30 January 2012
    Submission Date: 22 December 2011
    Release Date: 30 January 2012
    Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
    Patent pending: No
    Number of Pages: 121
    Institution: University of Pittsburgh
    Thesis Type: Doctoral Dissertation
    Refereed: Yes
    Degree: PhD - Doctor of Philosophy
    Uncontrolled Keywords: aflatoxin, liver cancer, hepatocellular carcinoma, hepatitis B, risk assessment, meta-analysis, systematic review
    Schools and Programs: Graduate School of Public Health > Environmental and Occupational Health
    Date Deposited: 30 Jan 2012 14:10
    Last Modified: 04 Jun 2013 11:24

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