Carcinogenesis Advance Access originally published online on November 24, 2006
Carcinogenesis 2007 28(5):995-999; doi:10.1093/carcin/bgl234
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Urinary 8-oxodeoxyguanosine, aflatoxin B1 exposure and hepatitis B virus infection and hepatocellular carcinoma in Taiwan
1 Departments of Environmental Health Sciences
2 Epidemiology
3 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, Taiwan
5 Present address: Graduate Institute of Aboriginal Health, Tzu Chi University, Hualien, Taiwan
6 Present address: Graduate Institute of Public Health, College of Medicine, Tzu Chi University, Hualien, Taiwan
7 Present address: Genomics Research Center, Academia Sinica, Taipei, 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 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 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 with subjects in the lowest quartile of 8-oxodG, there was a decrease in risk of HCC, with adjusted odds ratios (ORs) of 0.8 [95% confidence interval (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 second, third and fourth 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 with those with urinary 8-oxodG above the median and hepatitis B virus surface antigen 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.
Abbreviations: AFB1, aflatoxin B1; anti-HCV, antibodies against hepatitis C virus; BMI, body mass index; CI, confidence interval; HBsAg, hepatitis B virus surface antigen; HCC, hepatocellular carcinoma; 8-oxodG, 8-oxodeoxyguanosine; OR, odds ratio; PBS, phosphate-buffered saline; ROS, reactive oxygen species
Received August 23, 2006; revised November 6, 2006; accepted November 17, 2006.
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