Molecular biomarkers in type 2 diabetes and colorectal cancer

  • Ehsan Alvandi

Western Sydney University thesis: Doctoral thesis

Abstract

Globally, Type 2 Diabetes (T2D) and Colorectal Cancer (CRC) are among the most prevalent metabolic diseases and cancers, respectively. T2D is a progressive disease encompassing two underlying progressive conditions, insulin resistance and pancreas functional B-cell loss. CRC mostly arise from the aberrant proliferation of colonic epithelial cells in the form of colorectal polyps. T2D and CRC are chronic diseases and understanding the underlying molecular mechanism to identify biomarkers of their progression could help prevent or delay the course of the two diseases. Additionally, obesity is the major risk factor of T2D, and they are both considered as CRC risk factors. Therefore, there are common factors involved in the progression of T2D and CRC. In this regard, my thesis aimed to investigate T2D and CRC progression in four sections. Telomere length shortening is one of the hallmarks of cellular senescence. Shorter leukocyte telomere length in T2D has been reported previously. Firstly, I aimed to investigate cellular senescence and assess telomere biology using a cell model of human pancreas islet-derived progenitor cells (hIPCs). The second section studied was on how T2D progression was related to gut hormones regulating the insulin secretion from pancreas islets. Thirdly, SCFA was studied in relation to CRC progression. By conducting a systematic review and meta-analysis, a link between faecal SCFA level and the risk and incidence of CRC was established. Finally, in the fourth section, the concerning rising incidence of early-onset CRC (EOCRC: CRC diagnosed earlier than 50 years of age) led us to investigate this further by analysing a consecutive series of 3609 patients that underwent colorectal surgery over a 26-year period at Concord Hospital (NSW, Australia). The focus was on the incidence trend, clinicopathological features and survival in this age group. The current National Bowel Cancer Screening Program commences at the age of 50 years. Our findings including a significantly higher percentage of metastasis in EOCRC, as well as significantly higher risk of developing an advanced tumour in this age group provides supporting evidence for lowering the commencement age for CRC screening.
Date of Award2023
Original languageEnglish

Keywords

  • type 2 diabetes
  • rectum
  • cancer
  • biochemical markers
  • genetic aspects

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