Carcinogenesis Advance Access published online on November 24, 2006
Carcinogenesis, doi:10.1093/carcin/bgl234
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1 Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, NY
* To whom correspondence should be addressed. To evaluate the role of oxidative stress and aflatoxin exposure on risk of hepaotcellular carcinoma (HCC), a case-control study nested within a community based cohort was conducted in Taiwan. Baseline urine samples, collected from a total of 74 HCC cases and 290 matched controls, were used to determine by enzyme-linked immunosorbent assays the level of urinary excretion of 8-oxodeoxyguanosine (8-oxodG), a biomarker of oxidative DNA damage, and urinary aflatoxin B1 (AFB1) metabolites, a biomarker of aflatoxin exposure. Multivariate-adjusted linear regression analysis showed that urinary aflatoxin metabolites and gender were significantly associated with level of urinary 8-oxodG among controls. Moreover, after adjustments for potential confounding factors, there was a statistically significant positive dose-response relationship between levels of urinary 8-oxodG and urinary aflatoxin metabolites (p<0.0001). However, when compared to subjects in the lowest quartile of 8-oxodG, there was a decrease in risk of HCC, with adjusted ORs of 0.8 (95% CI 0.3-2.0), 0.7 (95% CI 0.3-2.0) and 0.7 (95% CI 0.2-1.7) for subjects in the 2nd, 3rd, and 4th quartile, respectively. The combination of level of urinary 8-oxodG below the median and hepatitis B virus infection resulted in an OR of 11.4 (95%CI=3.9-33.3), compared to those with urinary 8-oxodG above the median and HBsAg negative. These results suggest that elevated levels of urinary 8-oxodG may be related to increasing level of aflatoxin exposure but may also indicate enhanced repair of oxidative DNA damage and therefore lower risk of HCC.
Received August 23, 2006
Revised November 6, 2006
Accepted November 17, 2006
MOLECULAR EPIDEMIOLOGY
Urinary 8-oxodeoxyguanosine, Aflatoxin B1 Exposure and Hepatitis B Virus Infection and Hepatocellular Carcinoma in Taiwan
Hui-Chen Wu 1, Qiao Wang 1, Lian-Wen Wang 1, Hwai-I Yang 2, Habibul Ahsan 3, Wei-Yann Tsai 4, Li-Yu Wang 5, Shu-Yuan Chen 6, Chien-Jen Chen 7, and Regina M. Santella 1 *
2 Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
3 Department of Epidemiology, Mailman School of Public Health of Columbia University, New York, NY
4 Department of Biostatistics, Mailman School of Public Health of Columbia University, New York, NY
5 Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, NY; current address Graduate Institute of Aboriginal Health, Tzu Chi University, Hualien, Taiwan
6 Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, NY; current address Graduate Institute of Public Health, College of Medicine, Tzu Chi University, Hualien, Taiwan
7 Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan; current address Genomics Research Center, Academia Sinica, Taipei, Taiwan
Regina M. Santella, E-mail: rps1{at}columbia.edu
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