Detection of CYP2E1,a Genetic Biomarker of Susceptibility to Benzene Metabolism Toxicity in Immortal Human Lymphocytes Derived from the Han Chinese Population

Objective Cytochrome P450 2E1 （CYP2E1） is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia, We aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an efficient tool for detecting genetic biomarkers. Methods Immortalized human lymphocyte cell lines with independent genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by Single-Cell Gel Electrophoresis （SCGE）. Results Among the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of ~YP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene expression genotypes also showed higher comet rates compared with lower gene expression genotypes. Conclusion These results suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic biomarkers of susceptibility to chemicals.

Genetic screening of liver cancer:State of the art

Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.

Old-fashioned and newly discovered biomarkers:the future of NAFLD-related HCC screening and monitoring

Nonalcoholic fatty liver disease(NAFLD)is the major contributor to the global burden of chronic liver diseases and ranges from simple and reversible steatosis to nonalcoholic steatohepatitis(NASH),which may progress into cirrhosis and hepatocellular carcinoma(HCC).HCC represents the most common liver cancer,and it is a leading cause of death worldwide with an increasing trend for the future.Due to late diagnosis,non-responsiveness to systemic therapy,and high cancer heterogeneity,the treatment of this malignancy is challenging.To date,liver biopsy and ultrasound(US)are the gold standard procedures for HCC diagnosis and surveillance,although they are not suitable for mass screening.Therefore,it is impelling to find new,less invasive diagnostic strategies able to detect HCC at an early stage as well as monitor tumor progression and recurrence.Common and rare inherited variations that boost the switching from NASH to liver cancer may help to predict tumor onset.Furthermore,epigenetic changes which reflect intertumoral heterogeneity occur early in tumorigenesis and are highly stable under pathologic conditions.The severity of hepatic injuries can be detected through the analysis of cell circulating tumor DNAs(ctDNAs),microRNAs(miRNAs),and noncoding RNAs(ncRNAs),which are involved in several pathological processes that feature cancer,including cell growth,survival,and differentiation,thus representing appealing biomarkers for HCC.Therefore,this review discusses the current options for HCC surveillance,focusing on the role of genetic and epigenetic biomarkers as new strategies to refine HCC management.