Prediagnostic Level of Dietary and Urinary Isoflavonoids in Relation to Risk of Liver Cancer in Shanghai, China

Background: No epidemiologic studies have directly assessed the association between dietary and urinary isoflavonoids and risk of liver cancer in humans. Methods: A nested case-control study, including 217 incident cases of liver cancer and 427 individually matched control subjects, was conducted in Shanghai, China. Dietary isoflavonoid intakes were assessed through a validated food-frequency questionnaire and the Chinese Food Composition Tables. Urinary excretion levels of four major isoflavonoids were measured by the reversed- phase high-performance liquid chromatography. ORs and 95% confidence intervals (CI) were derived using conditional logistic regression models. Results: The adjusted ORs (95% CIs) for liver cancer across increasing quartiles of urinary genistein levels were 1.00 (reference), 0.55 (95% CI, 0.22-1.36), 0.57 (95% CI, 0.23-1.43), and 0.19 (95% CI, 0.06-0.59) (P-trend = 0.008) in women and 1.00 (reference), 1.22 (0.52-2.86), 1.17(0.47-2.90), and 1.23 (0.55-2.76) in men, respectively. These associations were consistent by limiting the cases to primary malignant neoplasm of liver or malignant neoplasms of the intrahepatic bile ducts, or among participants without self-reported liver disease or cirrhosis at the baseline survey. No associations were found between dietary isoflavonoids and liver cancer risk. Conclusions: Our study suggests for the first time that urinary excretion of genistein may be associated with reduced risk of liver cancer in women. Impact: In this nested case-control study in China, we found that urinary excretion of genistein was associated with lower risk of liver cancer in women, and not in men.