Genetic approaches to combating colorectal cancer

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Cancer of the large bowel, is a common and frequently fatal disease, affecting 43,000 people in the UK annually and causing ~16,000 deaths. Genes and environment both play a role in development of this cancer. Our research focuses on understanding the interplay of genes and environment on bowel cancer susceptibility and how these cause cancer at a molecular, cellular and whole-person level. We use state-of-the-art technologies to understand the complete picture of genetic and environmental effects on bowel cancer risk and find new genetic changes causally linked with cancer risk. This includes sequencing the entire genetic code (DNA) of human research subjects, and using genotyping arrays to tag parts of the human genetic makeup. We study the effects of these genetic variants in model systems from humans and animals. We aim to identify new ways to prevent cancers forming, and have begun clinical studies in humans to explore the beneficial effects of vitamin D on the lining of the human bowel. We are also able to change the genetic code in cells that we grow from the human bowel (intestinal organoids) using a system called “genome-editing”. This allows us to directly test the effects of genetic signals associated with cancer risk. We can also use genome editing approaches to reverse these effects and test the beneficial effects of drugs, and dietary components, on organoid and animal model systems. In future, we plan to test the effects of these agents in human studies. With our unique blend of discovery science, disease models and ability to translate laboratories findings to the clinic, we are extremely well-placed to make beneficial impact in human health in the field of a common cancer killer through early detection and cancer prevention.