Colon Cancer Genetics and Chemoprevention

 

Introduction

The over-arching mission of the Colon Cancer Genetics Group is to contribute to a reduction in incidence and mortality from cancer of the large bowel (colorectal cancer). Colorectal cancer is common (left image), and is second commonest cause of cancer death in the UK after lung cancer, being responsible for 16,000 deaths annually.

 

Fine mapping of 4 novel common genetic variants associated with colorectal cancer.

 

 

Research Links

• Online bowel cancer predictor
• Bowel cancer gene find could save thousands
• Genetic bowel cancer trigger found

 

Genes and Environmental Risk of Bowel Cancer

• Dietary Fatty Acids and Colorectal Cancer: A Case-Control Study
  
• Dietary Flavonoids and the Risk of Colorectal Cancer
  
• Aspirin activates the NF-B signalling pathway and induces apoptosis in intestinal neoplasia in two in vivo models of human colorectal cancer
  
• Bowel Cancer Risk Gene Pinpointed

 

 

Lab Members

Current lab members involved in this work are:

• Professor Malcolm G Dunlop
• Dr Susan M Farrington
• Dr Lesley Stark
• Dr Albert Tenesa
• Ms Farhat Din
• Dr Hazel Thoms
• Marion Walker
• Asta Valanciute
• Jim Simpson
• Nicole Gnadt
• Nicola Cartwright
• Ruth Wilson

 

1. Chemoprevention of Colorectal Cancer:
   Dr Lesley Stark
2. Cancer Genetics (Edinburgh Cancer Research Centre)
3. Publications

 

 

 

To achieve our research end, there are two main research strands:

1. Elucidating the genetic architecture of colorectal cancer
2. Understanding molecular mechanisms responsible for the chemopreventative properties of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs).

 

The research focus on the genetic basis of colorectal cancer aims to shed new light on disease causation and to combat the disease through preventative approaches and early detection. Genetic studies include investigation of the effect and contribution of known susceptibility alleles as well as to identify novel cancer predisposition genes. We are engaged in population-based studies amounting to several thousand patients and controls from Scotland, cancer families and highly enriched patient groups with extreme phenotype colorectal cancer. We have undertaken a genome-wide scan for low penetrance alleles in colorectal cancer and this has led to the identification of 10 common genetic variants thus far (February 2009). We are now pursuing the basis of cancer susceptibility through functional studies for a number of these associations. We are also applying these findings in risk prediction models to begin to develop population risk stratification approaches.

 

Cancer chemoprevention is another central theme of the group, focussed primarily on the effect of aspirin and other nonsteroidal anti-inflammatory drugs on NF-kappa-B signaling as a key mechanism of the anti-tumour effect of these agents. However, other pathways are also under investigation using basic molecular and cell biology, animal studies and clinical translational studies in patients. We are also studying patients at high risk of colorectal cancer due genetic predisposition.