Critical role of p53 gene mutation in ulcerative colitis-driving carcinogenesis.

Project: Research project

Project Details

Description

Overall objective of this study is to determine the mutation spectrum and load of an important tumor suppressor gene p53 in the patients with long-standing ulcerative colitis (UC) using the immunohistochemistry (IHC) and next-generation sequencing (NGS) approaches and to identify if the specific p53 mutation is critical in driving UC-induced carcinogenesis, particularly on evaluating its role as an efficient biomarker to predict the risk of cancer development in UC patients. Chronic inflammation is one of the most important risk factors contributing to human cancer [1, 2]. UC is a typical disease of
chronic inflammation associated with an increased risk for the development of cancer. The cumulative risk of cancer development increases with disease duration [3, 4]. Colorectal cancer (CRC) occurs in 2% of patients with UC after 10 years and 19% after 30 years. Compared to the general population, UC patients have an overall 11-fold relative risk of cancer and a 38-fold increased risk if UC is diagnosed before the age of 30 [5]. Several aspects of the chronic inflammatory process, including the overproduction of reactive oxygen species (ROS) and nitrogen species (RONS), overproduction/activation of key arachidonic acid (AA) metabolites and cytokines/growth factors and their activated signal transduction pathways may contribute to increased cancer risk [1, 6]. The most importance is that these inflammatory process results in DNA damage and genetic alterations/instability. Thus, identification of crucial inflammation-associated molecular events offers attractive targets and biomarkers for the prediction of cancer risk and for the prevention of this malignant disease.
StatusActive
Effective start/end date6/1/2012/31/21

Funding

  • Northwestern Memorial Hospital (#21)
  • Digestive Health Foundation (#21)

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