The role of E-cadherin expression and polymorphism in the development and progression of colorectal cancer

• Main Author: Lacy-Colson, Jon
• Format: Dissertation
• Language: English
• Published: Keele University 2008

Colorectal cancer represents a major disease burden worldwide in terms of both morbidity and mortality. Interestingly the primary tumour itself is rarely directly responsible for the patient's death but rather this comes about more usually as a result of distant metastatic disease. Understanding the mechanisms underlying the development of these metastases is therefore an important area for research. It has been shown that a decrease in the expression of E-cadherin is associated with an increased metastatic potential in a variety of epithelial tumours including colorectal cancer. Single nucleotide polymorphisms have been shown to play an important role in tumourigenesis. The purpose of this thesis therefore was to investigate the potential role of polymorphisms in the gene encoding E-cadherin (CDH1) in the progression of colorectal cancer to the metastatic phenotype. The CDH1-160 promoter polymorphism was significantly associated with an increased metastatic potential in colorectal cancers. We looked at three other polymorphisms within the CDH1 promoter and found no further associations with disease progression or susceptibility, either for the individual polymorphisms or for any particular haplotypes. We looked at direct haplotypes using multiple double ARMS PCR. We also conducted a meta-analysis which showed an association between decreased E-cadherin expression and disease progression. This work suggests an important role for CDH1 and promoter polymorphisms thereof in disease progression in colorectal cancer. This highlights a potential role for CDHI polymorphism as a potential prognostic indicator, and suggests that further work in this area might be fruitful in further elucidating the mechanisms underlying metastatic spread of colorectal (and perhaps other epithelial) cancers.