Population attributable risk of aflatoxin-related liver cancer: systematic review and meta-analysis

Eur J Cancer. 2012 Sep;48(14):2125-36. doi: 10.1016/j.ejca.2012.02.009. Epub 2012 Mar 8.


Background: Over 4 billion people worldwide are exposed to dietary aflatoxins, which cause liver cancer (hepatocellular carcinoma, HCC) in humans. However, the population attributable risk (PAR) of aflatoxin-related HCC remains unclear.

Methods: In our systematic review and meta-analysis of epidemiological studies, 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: Seventeen studies with 1680 HCC cases and 3052 controls were identified from 479 articles. All eligible studies were conducted in China, Taiwan, or sub-Saharan Africa. The PAR of aflatoxin-related HCC was estimated at 17% (14-19%) overall, 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 summarised 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%). The PAR has decreased over time in certain Taiwanese and Chinese populations.

Conclusions: In high exposure areas, aflatoxin multiplicatively interacts with HBV to induce HCC; reducing aflatoxin exposure to non-detectable levels could reduce HCC cases in high-risk areas by about 23%. The decreasing PAR of aflatoxin-related HCC reflects the benefits of public health interventions to reduce aflatoxin and HBV.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aflatoxins / adverse effects*
  • Africa South of the Sahara / epidemiology
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Carcinoma, Hepatocellular / epidemiology*
  • Carcinoma, Hepatocellular / virology
  • Case-Control Studies
  • China / epidemiology
  • Female
  • Food Contamination*
  • Hepatitis B / diagnosis
  • Hepatitis B / epidemiology
  • Hepatitis B Surface Antigens / blood
  • Humans
  • Liver Neoplasms / epidemiology*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk Assessment
  • Risk Factors
  • Taiwan / epidemiology
  • Young Adult


  • Aflatoxins
  • Biomarkers
  • Hepatitis B Surface Antigens