IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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IARC MONOGRAPHS VOLUME 82
aflatoxins was sometimes assessed via dietary questionnaires and sometimes via biomarker
measurements. As both of these were collected after disease onset, their relevance
to past lifetime intake of aflatoxins was uncertain. Beginning in the mid 1980s, some
prospective cohort studies were undertaken which avoided many of the methodological
limitations of earlier studies. Among the major advantages of this new generation of
studies were the following: new improved biomarkers of aflatoxin exposure, improved
ability to measure hepatitis infection, better comparability of cases and controls within a
well defined cohort, and control of the temporal sequence by measuring exposure before
disease onset.
In 1992, an IARC Working Group described all relevant human studies that had been
reported and concluded that there was sufficient evidence in humans for carcinogenicity
of aflatoxin B 1 and of naturally-occurring mixtures of aflatoxins. The present monograph
represents an update of evidence published since that evaluation was made, without
describing the studies covered in the previous monograph, although brief summaries of
the main studies are given in tabular format (Tables 10–12). These tables also provide
summaries of the relevant studies that have been published since 1993 and which are
described in the following sections. The outcome investigated in most studies was liver
cancer. Different studies used different sources (e.g., death certificates, hospital
registries, medical examinations) and different criteria (clinical, cytological) for definition
of liver cancer. Different terms, such as liver cancer, primary liver cancer or
hepatocellular carcinoma (HCC) were used. In the following descriptions, we have used
the terminology used by the authors.
2.1 Descriptive studies (see Table 10)
Hatch et al. (1993) conducted a hybrid ecological cross-sectional study in eight areas
of Taiwan (China), with a wide range of rates of mortality from primary hepatocellular
carcinoma (HCC). In order to derive estimates of aflatoxin levels in the eight areas, they
selected a representative sample of 250 adult residents in total (unequal numbers per
area). Participants were interviewed and were asked to provide both morning urine and
blood specimens. Serum was used for detecting hepatitis B surface antigen (HBsAg).
Urine was used for detecting aflatoxins B 1 and G 1 and metabolites, including aflatoxins
M 1 and P 1; the highest sensitivity was for aflatoxin B 1 . Measured values ranged from 0.7
to 511.7 pg equivalents of aflatoxin B 1/mL of urine, with a mean of 41.3 pg/mL. Mean
levels were similar in men and women, and in hepatitis B virus (HBV) carriers and HBV
non-carriers. The primary analyses were carried out with individuals as the unit of
analysis. In these analyses, the individual’s measurements of aflatoxin B 1 equivalents and
of HBsAg were used in conjunction with the HCC rate (sex-specific, age-adjusted) of the
entire area in which the individual resided. There were 246 data points for these analyses
(four individuals had missing blood specimens). Some bivariate correlation coefficients
and some regression analyses in which aflatoxin levels were regressed on area HCC
mortality, HBsAg, age and sex were calculated. In addition, in some analyses the data