Urinary 8-oxodeoxyguanosine, aflatoxin B1 exposure and hepatitis B virus infection and hepatocellular carcinoma in Taiwan.
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 B(1) 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.
Wu
Hui-Chen
HC
Departments of Environmental Health Sciences, Mailman School of Public Health of Columbia University, New York, NY 10032, USA.
Wang
Qiao
Q
Wang
Lian-Wen
LW
Yang
Hwai-I
HI
Ahsan
Habibul
H
Tsai
Wei-Yann
WY
Wang
Li-Yu
LY
Chen
Shu-Yuan
SY
Chen
Chien-Jen
CJ
Santella
Regina M
RM
D000328:Adult; D016604:Aflatoxin B1 / Q000633:toxicity* / Q000652:urine; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D004249:DNA Damage; D003838:Deoxyadenine Nucleotides / Q000652:urine*; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012306:Risk; D012737:Sex Factors; D013624:Taiwan
C089930:8-oxodeoxyadenosine triphosphate; D003838:Deoxyadenine Nucleotides; D016604:Aflatoxin B1