Abstract
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.
Highlights
In a previous prospective study in Taiwan, using biomarkers to assess exposure to aflatoxin B1 (AFB1) we demonstrated that the presence of AFB1-albumin adducts as well as urinary AFB1 metabolites were associated with increased risk of hepatocellular carcinoma (HCC) [2]
Urinary AFB1 metabolites were detectable in 97.3% (72 of 74) and 98.3% (285 of 290) HCC cases, and controls, respectively
We investigated the relative contributions of environmental determinants to the concentration of urinary excretion of 8-oxodG in a wellcharacterized Chinese adult population living in an area with high AFB1 exposure
Summary
The specific aims of this study were to investigate, among subjects without HCC, whether oxidative DNA damage, as assessed by urinary excretion 8-oxodG, is associated with AFB1 exposure, as assessed by urinary AFB1 metabolites and to examine the role of urinary 8-oxodG levels in HCC risk using data and biospecimens collected in a community-based Cancer Screening Program cohort
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