Colorectal cancer is a major public health challenge. While killing thousands of Canadians each year, mortality and severe morbidity due to the disease is potentially highly preventable through detection and treatment of precursor lesions and early stage disease. A large portion of individual risk for colorectal cancer is genetically inherited. While this was determined from family studies, only recently have individual genetic variants been identified through direct study of the genomes of those affected. Our team contains talented and experienced cancer researchers. The senior applicants, Drs. Hudson and Gallinger have worked together with other Canadian, US, and UK scientists in identifying several chromosomal regions that harbour genes that predispose to colorectal cancer. Drs. Lemire and Peltekova were recruited to the Ontario Institute for Cancer Research to bring statistical and molecular genetics expertise needed to refine the information derived from the genomic screens and pinpoint the specific genes and mutations involved in colon cancer. With the support of the Canadian Institutes of Health Research, the applicants will will identify and characterize new genetic determinants of risk. This may be used in the development of screening programs for high risk individuals and inform scientists on the biology of colon cancer (particularly early lesions) that may be used in future treatment strategies.