Carcinogenesis Advance Access originally published online on February 28, 2008
Carcinogenesis 2008 29(5):971-976; doi:10.1093/carcin/bgn057
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Urinary 15-F2t-isoprostane, aflatoxin B1 exposure and hepatitis B virus infection and hepatocellular carcinoma in Taiwan
1 Department of Environmental Health Sciences
2 Department of Epidemiology
3 Department of Biostatistics, Mailman School of Public Health of Columbia University, New York, NY 10032, USA
4 Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei 10617, Taiwan
5 Department of Statistics, National Chen Kung University Taiwan 701, Taiwan
6 Present address: Graduate Institute of Aboriginal Health, Tzu Chi University, Hualien 970, Taiwan
7 Present address: Graduate Institute of Public Health, College of Medicine, Hualien 970, Taiwan
8 Present address: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan
* To whom correspondence should be addressed. Tel: +1 212 305 1996; Fax: +1 212 305 5328; Email: rps1{at}columbia.edu
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-F2t-isoprostane (15-F2t-IsoP), a biomarker of lipid peroxidation. These samples had been previously analyzed for urinary aflatoxin B1 (AFB1) metabolites and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Pearson partial correlation coefficient analysis showed that urinary AFB1 metabolites and 8-oxodG were significantly associated with the level of urinary 15-F2t-IsoP. After adjustment for potential confounding factors in a conditional logistic regression model, urinary 15-F2t-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-F2t-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-F2t-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-F2t-IsoP and without HBV infection. These results suggest that elevated levels of urinary 15-F2t-IsoP may be related to increasing level of aflatoxin exposure and are associated with an increased risk of HCC.
Abbreviations: AFB1, aflatoxin B1; AFP, 
-fetoprotein; BMI, body mass index; CI, confidence interval; 15-F2t-IsoP, 15-F2t-isoprostane; HBsAg, hepatitis B virus surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; IsoP, F2-isoprostane; OR, odds ratio; 8-oxodG, 8-oxo-7,8-dihydro-2'-deoxyguanosine; ROS, reactive oxygen species
Received November 5, 2007; revised February 15, 2008; accepted February 15, 2008.