Dieckmann, Amanda (2016) The effects of a high carbohydrate and high fat diet and dietary interventions in the molecular tumourigenesis of colorectal cancer. Honours thesis, University of Southern Queensland. (Unpublished)
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Text (Whole Thesis)
The Effects of a High Carbohydrate and High Fat Diet on the molecular Tumourigenesis of Colorectal Cancer Amanda Dieckmann.pdf Download (1MB) | Preview |
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Text (Honours Dissertation Submission Form)
Honours Dissertation Submission form Amanda Dieckmann.pdf Restricted |
Abstract
Colorectal cancer (CRC) is the most commonly diagnosed cancer affecting both men and women in Australia. The Epidermal Growth Factor Receptor (EGFR) plays an important role in the development and progression of CRC. EGFR regulates a number of essential cellular processes including proliferation, migration, differentiation and survival however the overexpression of EGFR is a major driver of CRC tumourigenesis. Numerous studies have demonstrated that there is a strong association between a high carbohydrate and high fat diet (HCHF), EGFR expression and the tumourigenesis of CRC. One of the activators of EGFR signalling is A disintegrin and metalloprotease domain 17 (ADAM17) and this protein has also been implicated in high fat diet induced CRC. One of ADAM17’s roles is the proteolytic cleavage of EGFR activating ligands including the transforming growth factor alpha (TGFα).
Curcumin has demonstrated promising anti-inflammatory, antineoplastic, antioxidant and chemopreventative properties in the colon and has been shown to suppress the growth of colon cancer cells in animal models and human cell culture. The effectiveness of curcumin in reducing the expression of CRC biomarkers caused by a HCHF diet has not yet been investigated but may prove to be an effective strategy for preventing CRC.
This study provided evidence that a HCHF diet significantly increases the mRNA expression of the CRC biomarkers EGFR, ADAM17 and TGFα in the distal colon tissue obtained from rats fed a HCHF diet compared to those fed a normal corn starch diet. Furthermore, it demonstrated that the effects of these changes could be prevented by supplementing the HCHF diet with 100 mg/kg body mass of curcumin. A preliminary experiment also found that the molecular changes that occurred in response to the HCHF diet could be driven by the aberrant expression of epigenetic modifying enzymes. Understanding the mechanisms by which diet regulates tumourigenic changes in the colon is vitally important as diet is modifiable and may be a crucial target for preventing high fat diet induced CRC or at least reducing risk.
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