8-epi-prostaglandin-f2alpha and Carcinoma--Hepatocellular

Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of hepatocellular carcinoma (HCC). We conducted a nested case-control study of 347 HCC cases and 691 matched controls within a prospective cohort of 18 244 Chinese men in Shanghai, China. The concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α), a biomarker of oxidative stress, and prostaglandin E2 (PGE2) metabolite (PGE-M), a biomarker of the inflammation mediator PGE2, were determined in baseline urine samples using validated mass spectrometry assays. 8-epi-PGF2α levels were significantly higher in HCC cases than control subjects (geometric means 0.92 versus 0.80 pmol/mg creatinine, P < 0.001). The relative risks of developing HCC for the highest relative to the lowest quartile of 8-epi-PGF2α were 2.55 (95% confidence interval = 1.62-4.01, Ptrend < 0.001). This positive 8-epi-PGF2α-HCC risk association was independent of smoking status, alcohol consumption and hepatitis B or liver cirrhosis and was present 10 years before the clinical manifestation of HCC. This study did not find any significant association between urinary PEG-M and HCC risk. This study provides direct evidence in support of the critical role of oxidative stress in the development of HCC regardless of its underlying causes.

Topics: Biomarkers, Tumor; Body Mass Index; Carcinoma, Hepatocellular; Case-Control Studies; China; Cohort Studies; Dinoprost; Dinoprostone; Female; Humans; Inflammation; Liver Neoplasms; Male; Middle Aged; Oxidative Stress; Risk Factors

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-F(2t)-isoprostane (15-F(2t)-IsoP), a biomarker of lipid peroxidation. These samples had been previously analyzed for urinary aflatoxin B(1) (AFB(1)) metabolites and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Pearson partial correlation coefficient analysis showed that urinary AFB(1) metabolites and 8-oxodG were significantly associated with the level of urinary 15-F(2t)-IsoP. After adjustment for potential confounding factors in a conditional logistic regression model, urinary 15-F(2t)-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 with subjects in the lowest tertile of 15-F(2t)-IsoP, there was a trend of increasing risk of HCC (P(trend) = 0.0008), with adjusted ORs (95% CIs) of 3.87 (1.32-11.38) and 6.27 (2.17-18.13) for the second and third tertile, respectively. In addition, the combination of urinary 15-F(2t)-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 with those with low urinary 15-F(2t)-IsoP and without HBV infection. These results suggest that elevated levels of urinary 15-F(2t)-IsoP may be related to increasing level of aflatoxin exposure and are associated with an increased risk of HCC.

Topics: Aflatoxin B1; Biomarkers; Carcinoma, Hepatocellular; Death Certificates; Dinoprost; Hepatitis B; Humans; Interviews as Topic; Lipid Peroxidation; Liver Neoplasms; Mass Screening; Odds Ratio; Reference Values; Registries; Taiwan