A FOLLOW-UP-STUDY OF URINARY MARKERS OF AFLATOXIN EXPOSURE AND LIVER-CANCER RISK IN SHANGHAI, PEOPLES-REPUBLIC-OF-CHINA

A cohort of 18,244 mostly middle-aged (45-64 years) men residing in fo ur small geographically defined areas of Shanghai was accrued between January 1986 and September 1989. In addition to an in-person interview regarding dietary and other past exposures, each subject donated a si ngle void urine sample at recruitment so that the presence of aflatoxi ns in urine could be assessed. In addition, a 1-year survey of market foods in Shanghai was conducted to quantitatively estimate the extent of aflatoxin exposure in the study population. After close to 70,000 p erson-years of follow-up, 55 incident cases of hepatocellular carcinom a (HCC) had been identified. Levels of urinary aflatoxin B-1 and the o xidative metabolites, including the major aflatoxin nucleic acid adduc t, aflatoxin-N-7-guanine, were determined for 50 of the 55 identified cases of HCC. Two hundred sixty-seven controls were chosen randomly fr om the cohort; they were matched to the 50 cases by age (within 1 year ), time of specimen collection (within 1 month), and residence. After integrating the high-pressure liquid chromatography chromatograms to m easure aflatoxin-N-7-guanine, aflatoxin M(1), aflatoxin P-1, and aflat oxin B-1, 49, 67, 53, and 71 of the urine samples had detectable level s of these compounds, respectively. The aflatoxin metabolite detected at the highest concentration was aflatoxin P-1; the range was 0.59-16. 0 ng/ml. The range of aflatoxin M, in the urine was 0.17-5.2 ng/ml. Th e aflatoxin-N-7-guanine adduct range was 0.3-1.81 ng/ml in the 49 posi tive samples. A nested case-control analysis showed highly significant associations between the presence of urinary aflatoxins, serum hepati tis B surface antigen positivity, and HCC risk. Risk was especially el evated in individuals who were positive for both of these biomarkers ( relative risk = 59.4; 95% confidence limit, 16.6, 212.0 after adjustme nt for cigarette smoking, a potential confounder). On the other hand, a cohort analysis using all 55 cases of HCC revealed no strong or stat istically significant association between HCC risk and dietary aflatox in consumption as determined from the in-person food frequency intervi ew combined with the survey of market foods in the study region. Our r esults underline the importance of biomarker measurements in assessing the aflatoxin-HCC association in epidemiological studies.