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Drinking mutagenic downstream water from the Huangpu River was hypothesized to have increased the risk for male esophageal cancer in Shanghai, China. The authors conducted a population-based case-control study of a total of 71 esophageal cancer deaths and 1,122 controls collected during a 5-year follow-up period, 1984-1988, from four male cohorts born before January 1, 1944, living in four communities consuming water with different mutagenicities in the Shanghai area. The controls represented a 1% random sample of the defined living cohorts selected at the end of each of the 5 years of follow-up. Logistic regression showed an odds ratio of 2.77 (95% confidence interval: 1.52, 5.03) for drinking mutagenic downstream water from the river versus drinking nonmutagenic upstream water after controlling for possible confounders including age, disease history (hepatitis, cirrhosis, schistosomiasis, digestive tract ulcer), hazardous occupational history, pesticide exposure, lifestyle factors (cigarette smoking, tea intake, and alcohol intake), dietary habits (intake of pickled vegetables, maize, peanuts, and cured meat), education, poverty, urban environment, and water chlorination.