IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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IARC MONOGRAPHS VOLUME 82
residence and date of recruitment to one or two randomly selected HBsAg-positive
controls (total, 149). Blood samples were collected and analysed for HBV and HCV, for
aflatoxin B 1–albumin adducts, and for glutathione S-transferase (GST) M1 and T1 genotypes.
In a conditional logistic regression analysis, a significant relationship was
observed between HCC risk and aflatoxin B 1–albumin adducts (OR = 2.0; 95% CI,
1.1–3.7). GSTM1- and GSTT1-null genotypes were associated with a decreased risk for
HCC (OR = 0.4; 95% CI, 0.2–0.7 and OR = 0.5; 95% CI, 0.2–0.9). A statistically significant
(p = 0.03) interaction was found between aflatoxin B 1–albumin adducts and
GSTT1 genotype, indicating a more pronounced risk among those who were GSTT1-null
genotype (OR = 3.7; 95% CI, 1.5–9.3), and no risk among those who had the non-null
genotype (OR = 0.9; 95% CI, 0.3–2.4).
Yu et al. (1997a) carried out a cohort study in Taiwan, China, to study the role of aflatoxin
in the etiology of HCC. Between 1988 and 1992, a cohort of 4841 male asymptomatic
HBsAg carriers and 2501 male non-carriers, aged 30–65 years, was recruited from
the Government Employee Central Clinics and the Liver Unit of a hospital in Taipei. At
entry into the study, each participant was interviewed to obtain information on demographic
characteristics, habits of cigarette smoking and alcohol drinking, diet (including
the frequency of consuming peanuts and fermented bean products, which are thought to
be the major aflatoxin-contaminated foodstuffs in Taiwan), as well as personal and
family history of major chronic diseases. Urine and blood samples from study subjects
were stored frozen. All HBsAg carriers in this study had both ultrasonography and αfetoprotein
measurement every 6–12 months. Follow-up of HBsAg non-carriers was
carried out by annual examination including a serum α-fetoprotein test. The response rate
to the periodic follow-up examinations was approximately 72% for HBsAg carriers and
80% for HBsAg non-carriers. Information on HCC occurrence and vital status of study
subjects who did not participate in the follow-up examinations was obtained from both
computerized data files of the national death certification and the cancer registry. By
31 December 1994, 34 579 person-years of follow-up had been accumulated, an average
of 4.7 years per person. Fifty HCC cases were identified during the follow-up period. All
HCC cases were diagnosed on the basis of either pathological and cytological examinations
or an elevated α-fetoprotein level combined with at least one positive image. To
investigate the role of aflatoxin, a nested case–control comparison was carried out, in
which two separate matched controls per case were selected, one who was HBsAgpositive
and one who was HBsAg-negative. Levels of aflatoxin metabolites in urine were
analysed by reverse-phase HPLC allowing measurement of aflatoxins M 1, P 1, B 1 and G 1
and aflatoxin B 1–N7-guanine. Most subjects were also tested for anti-HCV. After exclusion
of subjects with missing specimens, analyses were available on 43 matched case–
control sets. Among all HCC cases, only one occurred in the HBsAg-negative subcohort,
and that one was positive for anti-HCV. All study subjects were positive for aflatoxin M 1,
81% for aflatoxin P 1, 43% for aflatoxin B 1–N7-guanine adducts, 28% for aflatoxin B 1
and 12% for aflatoxin G 1. There was a significant correlation (r = 0.35) between reported
dietary intake of various foods thought to contain aflatoxins and levels of urinary