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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 F 2α  (8- epi -PGF 2α ), a biomarker of oxidative stress, and prostaglandin E 2  (PGE 2 ) metabolite (PGE-M), a biomarker of the inflammation mediator PGE 2 , were determined in baseline urine samples using validated mass spectrometry assays. 8- epi- PGF 2α  levels were significantly higher in HCC cases than control subjects (geometric means 0.92 versus 0.80 pmol/mg creatinine,  P  &lt; 0.001). The relative risks of developing HCC for the highest relative to the lowest quartile of 8- epi- PGF 2α  were 2.55 (95% confidence interval = 1.62–4.01,  P  trend  &lt; 0.001). This positive 8- epi -PGF 2α –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.

carcinogenesis

Prediagnostic levels of urinary 8- epi -prostaglandin F 2α  and prostaglandin E 2  metabolite, biomarkers of oxidative damage and inflammation, and risk of hepatocellular carcinoma