Prediagnostic levels of urinary 8-epi-prostaglandin F2α and prostaglandin E2 metabolite, biomarkers of oxidative damage and inflammation, and risk of hepatocellular carcinoma. (5th January 2019)

• Record Type: Journal Article
• Authors: Yuan, Jian-Min; Grouls, Menno; Carmella, Steven G; Wang, Renwei; Heskin, Alisa; Jiang, Yang; Tan, Yu-Ting; Adams-Haduch, Jennifer; Gao, Yu-Tang; Hecht, Stephen S
• Is Part Of: Carcinogenesis. Volume 40:Number 8(2019)
• Page Start: 989
• Page End: 997
• Publication Date: 2019-01-05
• Subjects: Carcinogenesis -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Cancer -- Prevention -- Periodicals; Cancer -- Periodicals; 616.994071
• DOI: 10.1093/carcin/bgy180
• Languages: English
• ISSNs: 0143-3334

Abstract

Abstract: 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, P trend < 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.