IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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IARC MONOGRAPHS VOLUME 82
history based on a frequency checklist of 45 food items usually consumed as an adult was
combined with a set of independently measured aflatoxin levels in various local foods to
derive a quantitative measure of dietary aflatoxin exposure. In a cohort-type analysis,
using the lowest tertile of aflatoxin exposure as reference, the middle tertile had a relative
risk (adjusted for age and smoking) of 1.6 (95% confidence interval [CI], 0.8–3.1; 25
cases) and the highest tertile had an odds ratio (OR) of 0.9 (95% CI, 0.4–1.9; 16 cases).
To assess the risks in relation to biomarkers of aflatoxin exposure, a nested case–
control study was conducted using 50 of the cases (Qian et al., 1994). Controls were
selected from among subjects who had no history of liver cancer on the date of cancer
diagnosis of the index cases and were matched to cases in ratios ranging from 10:1 to 3:1,
yielding a total of 267 controls. For each case and control, urine samples were analysed
for aflatoxins B 1, P 1 and M 1 and for aflatoxin B 1–N7-guanine adducts, and among a subgroup
of 28 cases and their matched controls for aflatoxins G 1 and Q 1. HBsAg was
measured by radioimmunoassay. Thirty-two out of 50 cases and 31 out of 267 controls
were HBsAg-positive. Each of the six biomarkers of aflatoxin exposure was more
frequently present among cases than controls. For 36 of the 50 liver cancer cases and 109
of 267 controls, results were positive in at least one of the four assays analysed for the
full set of cases and controls (adjusted relative risk, 5.0; 95% CI, 2.1–12). The highest
risks were found among subjects with aflatoxin B 1–N7-guanine adducts. Compared with
subjects who had no aflatoxin biomarkers and were HBsAg-negative, the interaction of
the two factors was supra-multiplicative, with relative risks as follows: aflatoxin
biomarker only, 3.4 (95% CI, 1.1–10); HBsAg only, 7.3 (95% CI, 2.2–24); both factors,
59 (95% CI, 17–212). [The Working Group noted inconsistencies between analyses
based on dietary questionnaires and biomarkers.]
The Penghu Islets reportedly have the highest rates of HCC in Taiwan, China. Chen
et al. (1996) enrolled 4691 men and 1796 women, aged 30–65 years, in a prospective
cohort study. The subjects were selected from a housing register maintained by the local
administration. Participants were interviewed on a variety of sociodemographic, dietary
and medical history topics. Blood samples were collected and stored frozen. A two-stage
screening process for HCC was undertaken which included serological markers and
clinical assessments with ultrasonography. Subjects were further followed up with
annual examinations. A total of 33 cases of HCC were diagnosed by December 1993, of
whom two were negative for HBsAg. A total of 123 controls were selected from within
the cohort among unaffected subjects, and matched with cases for age, sex, village and
date of blood collection. Blood samples from cases and controls were analysed for
HBsAg, for anti-hepatitis C virus (HCV) antibodies and aflatoxin B 1–albumin adducts,
although samples for adduct analysis were usable for only 20 cases and 86 controls.
Using logistic regression, with age and sex adjustment, and a detection limit for albumin
adducts of 0.01 fmol/μg as the cut-off value, the OR for an association between presence
of aflatoxin B 1–albumin adducts and HCC was 3.2 (13 cases; 95% CI, 1.1–8.9). When
the statistical model also included several other covariates (HBsAg, anti-HCV, family
history of liver cancer and cirrhosis), the odds ratio for aflatoxin B 1–albumin adducts