Colorectal cancer is the second leading cause of cancer deaths in Canada. In 2009, an estimated 22,000 Canadians will be diagnosed with colorectal cancer and 9,100 will die from the disease.
The disease, however, usually grows slowly, almost always arising from benign growths called adenomas (or polyps). If these growths are detected early and removed, the disease is very treatable and curable, and even preventable.
Dr Will King hopes that his research will eventually improve those chances for preventing the disease. With funding from the Canadian Cancer Society, he is studying the relationship between certain genetic activity and the risk for colorectal adenomas.
Specifically, Dr King and his research team are studying DNA methylation, which refers to a chemical modification of the genetic material in cells. The researchers are interested in this process because DNA methylation plays an important role in controlling how cells behave and divide.
Previous research has used animal and human cells to investigate the relationship between DNA methylation and cancer. Dr King’s study will be one of the few studies that will involve human populations and is the largest of this kind to date.
The researchers will examine whether markers of DNA methylation in blood and colon tissue predict whether a person will develop colorectal cancer. Dr King’s group plans to measure these markers in blood and normal appearing colon tissue samples from 350 participants aged 50 to 65 who are undergoing a colonoscopy at the Hotel Dieu Colonoscopy Clinic in Kingston. The team will compare DNA methylation marker levels of patients with adenomas to those with no abnormality to determine whether abnormal levels of these markers are associated with an increased risk for developing colorectal adenoma.
"If we find a relationship between DNA methylation and colorectal adenomas, I think it would provide us tremendous opportunities for the prevention of colorectal cancer," says Dr King. "Rather than waiting for the occurrence of cancer, we would be able to identify individuals at high risk for colorectal cancer who could be targeted for intervention and screening programs."
DNA methylation is a key mechanism of the epigenome, described as the second genetic code. While our genes act as a kind of blueprint for designing our body – for example determining or hair colour or height – the epigenome provides the instructions by telling our genes what to do, where to do it and when to do it.
While scientists are still deciphering the epigenome, what is known is that numerous chemicals in our bodies control which sets of genes are switched on in any given cell. In effect, these chemicals give cells instructions on how they should function. The epigenome regulates this entire chemical switching system. When this process is disrupted, it can lead to the inappropriate turning on of genes, which in turn leads to inappropriate cell growth and ultimately cancer.
Dr King is at Queen’s University in Kingston. His three-year, $372,910 grant is his first from the Canadian Cancer Society.