IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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In a large cohort study in Shanghai, China, risk for hepatocellular carcinoma was
elevated among people with aflatoxin metabolites in urine, after adjustment for cigarette
smoking and hepatitis B surface antigen positivity. No association was observed between
dietary aflatoxin levels, as ascertained by a diet frequency questionnaire, and risk for
hepatocellular carcinoma.
There were four reports from cohort studies in Taiwan, China, although three of them
partly overlapped. Selected subjects in the three overlapping studies were enrolled, were
interviewed, had biological specimens taken, and were followed up intensively for liver
cancer. In nested case–control studies, including some prevalent cases, subjects with
exposure to aflatoxin, as assessed by biomarker measurements, had elevated risks for
liver cancer, after adjustment for hepatitis B surface antigen positivity. The effect due to
aflatoxin exposure was especially high among those who were positive for hepatitis B
surface antigen, but there were few liver cancer cases negative for hepatitis B surface
antigen. The other Taiwan study was carried out in a large cohort of chronic carriers of
hepatitis B virus. These subjects were interviewed at baseline, had biological specimens
taken, and were followed up intensively for liver cancer. Several aflatoxin metabolites
and albumin adducts were measured in a nested case–control series. Subjects with quantified
levels of most of the biomarkers of exposure to aflatoxin showed elevated risk for
liver cancer.
In two studies in Qidong, China, cohorts of hepatitis B carriers were tested for biomarkers
of aflatoxin and followed up for liver cancer. In both studies, subjects with aflatoxin
biomarkers had excess risks for liver cancer.
In a Sudanese case–control study of liver cancer, a relationship was found between
reported ingestion of peanut butter and liver cancer in a region with high aflatoxin contamination
of peanuts, but no such relationship in a region with low contamination of
peanuts.
In a hybrid ecological cross-sectional study in Taiwan, China, a number of subjects
were selected from eight regions; for each subject several biomarkers of aflatoxin and
hepatitis B viral infection were assessed in relation to the liver cancer rates in the region
of residence. There were correlations between aflatoxin metabolites and liver cancer
rates after adjustment for hepatitis B status.
The overall body of evidence supports a role of aflatoxins in liver cancer etiology,
notably among subjects who are carriers of hepatitis B surface antigen. Nevertheless, the
interpretation of human studies is hampered by the difficulties in properly assessing an
individual’s lifetime exposure to aflatoxins and the difficulties in disentangling the
effects of aflatoxins from those of hepatitis infections. Novel biomarkers, some still
under development and validation, should bring greater clarity to the issue.
5.3 Animal carcinogenicity data
IARC MONOGRAPHS VOLUME 82
Extensive experimental studies on the carcinogenicity of aflatoxins led to a previous
IARC Monographs evaluation of the evidence as follows: sufficient evidence for carcino-