Aflatoxin is not a probably human carcinogen: the published evidence is sufficient

Area of Science:

• Toxicology and Carcinogenesis
• Epidemiology and Public Health
• Hepatology and Viral Hepatitis

Background:

• Aflatoxin, a mold-derived food contaminant, has been investigated for its carcinogenic potential in humans since the 1960s.
• Early laboratory studies suggested species-specific differences in aflatoxin metabolism, implying humans might be refractory to its carcinogenic effects.
• Conflicting early epidemiological evidence and later strong associations between hepatitis B virus (HBV) infection and primary liver cancer (PLC) complicated the assessment of aflatoxin's role.

Purpose of the Study:

• To critically evaluate the evidence for aflatoxin as a probable human carcinogen, considering both laboratory and epidemiological data.
• To assess the confounding influence of hepatitis B virus (HBV) infection on epidemiological studies linking aflatoxin exposure to primary liver cancer (PLC).
• To re-examine the International Agency for Research on Cancer (IARC) conclusions regarding aflatoxin's carcinogenicity in light of updated scientific understanding.

Main Methods:

• Review and analysis of historical and contemporary laboratory studies on aflatoxin metabolism and carcinogenicity across species.
• Critical appraisal of epidemiological studies investigating the association between aflatoxin exposure and primary liver cancer (PLC).
• Evaluation of studies controlling for or assessing the impact of hepatitis B virus (HBV) infection as a confounding factor in aflatoxin-PLC research.

Main Results:

• Laboratory evidence suggests humans may be less susceptible to aflatoxin's oncogenic effects compared to other species.
• Early epidemiological studies were flawed, particularly by not accounting for the strong etiological link between HBV infection and PLC.
• Later studies, including those in the U.S. excluding HBV, and those in endemic areas attempting to control for HBV, failed to provide convincing evidence for a primary role of aflatoxin in human PLC induction.

Conclusions:

• The available epidemiological evidence, when properly controlled for HBV, does not support aflatoxin as a primary cause of human liver cancer.
• While an accessory role for aflatoxin in HBV-related liver cancer cannot be definitively excluded, it is not an essential condition.
• The IARC's 1987 conclusion classifying aflatoxin as a probable human carcinogen appears to be based on flawed or irrelevant evidence, overlooking critical confounding factors and species differences.