A Follow-Up Study of Urinary Markers of Aflatoxin Exposure and Liver Cancer Risk in Shanghai, People's Republic of China

Geng Sun Qian, Ronald K. Ross, Mimi C. Yu, Jian Min Yuan, Yu Tang Gao, Brian E. Henderson, Gerald N. Wogan, John D. Groopman

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575 Scopus citations


A cohort of 18,244 mostly middle-aged (45-64 years) men residing in four 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 single void urine sample at recruitment so that the presence of aflatoxins 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 person-years of follow-up, 55 incident cases of hepatocellular carcinoma (HCC) had been identified. Levels of urinary aflatoxin B1 and the oxidative metabolites, including the major aflatoxin nucleic acid adduct, aflatoxin-N7-guanine, were determined for 50 of the 55 identified cases of HCC. Two hundred sixty-seven controls were chosen randomly from 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 measure aflatoxin-N7-guanine, aflatoxin M1 aflatoxin P1, and aflatoxin B1 49, 67, 53, and 71 of the urine samples had detectable levels of these compounds, respectively. The aflatoxin metabolite detected at the highest concentration was aflatoxin P1; the range was 0.59-16.0 ng/ml. The range of aflatoxin M1 in the urine was 0.17-5.2 ng/ml. The aflatoxin-N7-guanine adduct range was 0.3-1.81 ng/ml in the 49 positive samples. A nested case-control analysis showed highly significant associations between the presence of urinary aflatoxins, serum hepatitis B surface antigen positivity, and HCC risk. Risk was especially elevated in individuals who were positive for both of these biomarkers (relative risk = 59.4; 95% confidence limit, 16.6, 212.0 after adjustment for cigarette smoking, a potential confounder). On the other hand, a cohort analysis using all 55 cases of HCC revealed no strong or statistically significant association between HCC risk and dietary aflatoxin consumption as determined from the in-person food frequency interview combined with the survey of market foods in the study region. Our results underline the importance of biomarker measurements in assessing the aflatoxin-HCC association in epidemiological studies.

Original languageEnglish (US)
Pages (from-to)3-10
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Issue number1
StatePublished - 1994

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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