Grant: Operating Grant

Although less than 5% of cancers are obviously hereditary, that is they are predominantly caused by inherited and not environmental factors, these cancer cases can often be prevented if the causative mutations (genetic changes) are known. Our team has shown that cancers can be prevented in the 45% of families with hereditary gastric cancer where we can find a mutation in the CDH1 gene. We are also developing screening and unique management plans for familial pancreatic cancer families with known mutations. In this study, we propose to find the mutations causing cancer in other unexplained upper GI cancers (esophageal, gastric, pancreatic and others). We will apply full genome sequencing (a state-of-the-art technique for deciphering an entire human DNA sequence) to make these discoveries. We will also examine the tumours to determine if mutations found are really causative of the cancers. We will test additional families for all mutations discovered and rapidly disseminate our discoveries internationally so that testing for new genes can become routine in clinical laboratories as soon as possible. We will also study the tumors from these families to see if they are distinct in terms of treatment opportunities compared to sporadic cancers. Through this research we will develop and disseminate tools to prevent cancers in families at high risk for upper GI cancer. The research team includes senior researchers, new and incoming recruits and trainees; we believe the project will provide great opportunities for mentorship of the junior members as they to build careers as clinician scientists and for the trainees who will work with us on this project.