Carcinogenesis Advance Access published online on February 28, 2008
Carcinogenesis, 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, Mailman School of Public Health of Columbia University, New York, NY
2 Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY
3 Department of Biostatistics, Mailman School of Public Health of Columbia University, New York, NY
4 Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
5 current address Graduate Institute of Aboriginal Health, Tzu Chi University, Hualien, Taiwan
6 current address Graduate Institute of Public Health, College of Medicine, Hualien, Taiwan
7 current address Genomics Research Center, Academia Sinica, Taipei, Taiwan
8 Department of Statistics, National Chen Kung University, Taiwan
Corresponding author: Dr. Regina M. Santella, Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University,630 West 168th St., RM19-418 New York, NY 10032, USA, Phone 212 305-1996, Fax: 212 305-5328, E-mail: 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 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 to 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%CI) of 3.87 (1.32-11.38), and 6.27 (2.17-18.13) for the 2nd, and 3rd 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 to those with low urinary 15-F2t-IsoP and without HBV infection. These results suggest that elevated levels of urinary of 15-F2t-IsoP may be related to increasing level of aflatoxin exposure and are associated with an increased risk of HCC
Key Words: Hepatitis B virus • Hepatocellular carcinoma • Oxidative stress • Lipid peroxidation • Urinary aflatoxin metabolites • Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine • Urinary 15-F2t-Isoprostane
Received November 5, 2007; revised February 15, 2008; accepted February 15, 2008.
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