Urinary 15-F 2t -isoprostane, aflatoxin B 1 exposure and hepatitis B virus infection and hepatocellular carcinoma in Taiwan

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Abstract
To evaluate the role of oxidative stress and aflatoxin exposure on risk of hepatocellular carcinoma (HCC), a case–control study nested within a large community-based cohort was conducted in Taiwan. Baseline urine samples, collected from a total of 74 incident HCC cases and 290 matched controls, were used to determine by enzyme-linked immunosorbent assays the level of urinary 15-F 2t -isoprostane (15-F 2t -IsoP), a biomarker of lipid peroxidation. These samples had been previously analyzed for urinary aflatoxin B 1 (AFB 1 ) metabolites and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). Pearson partial correlation coefficient analysis showed that urinary AFB 1 metabolites and 8-oxodG were significantly associated with the level of urinary 15-F 2t -IsoP. After adjustment for potential confounding factors in a conditional logistic regression model, urinary 15-F 2t -IsoP was significantly associated with risk of HCC [above versus below the mean odds ratio (OR) = 2.53, 95% confidence interval (CI) = 1.30–4.93]. Moreover, when compared with subjects in the lowest tertile of 15-F 2t -IsoP, there was a trend of increasing risk of HCC ( Ptrend = 0.0008), with adjusted ORs (95% CIs) of 3.87 (1.32–11.38) and 6.27 (2.17–18.13) for the second and third tertile, respectively. In addition, the combination of urinary 15-F 2t -IsoP above the mean and chronic hepatitis B virus (HBV) infection resulted in an OR of 19.01 (95% CI = 6.67–54.17) compared with those with low urinary 15-F 2t -IsoP and without HBV infection. These results suggest that elevated levels of urinary 15-F 2t -IsoP may be related to increasing level of aflatoxin exposure and are associated with an increased risk of HCC.