Approved research

Identification of genomic and microenvironmental factors in high-risk populations for pancreatic cancer

Lay summary

In the UK, there were approximately 10 000 new cases of pancreatic cancer in 2015 and almost 9 300 deaths from pancreatic cancer in 2016. It is one of the deadliest forms of cancer, and incidence is on the rise in the UK and in other developed countries too. In fact, pancreatic cancer is expected to become the second leading cause of cancer-related mortality within the next decade if outcomes do not improve. One of the main reasons for this high mortality rate is the fact that pancreatic cancer is typically diagnosed in late stages when few treatment options are available. Another reason stems from our current inability to screen high-risk individuals. As a matter of fact, aside from age, several environmental factors have only been weakly associated with increased risk including diabetes mellitus type 2, obesity, chronic pancreatitis, smoking, and heavy alcoholism. Inherited genetic variants can also increase risk, but they explain just 2% of all cases. It is therefore imperative to find novel markers and risk predictors of pancreatic cancer. Our proposed work is aimed at addressing this major clinical challenge. Taking a hint from recent studies suggesting that in addition to cancer genetics, the immune system and pathogenic infections also contribute crucially to the development of pancreatic cancer, we have devised two-pronged analysis of the UK biobank resource. First, we plan to study associations between pancreatic cancer and inherited individual variants. Second, we focus on the significant comorbidities related to bacterial and viral infections, as well as the autoimmune disorders and allergies. Finally, we plan to integrate both types of factors in order to determine their joint contributions to risk and predicting pancreatic cancer diagnoses. If successful, our 24-month project can potentially deliver new means of predicting the risk of pancreatic and help screen highly susceptible individuals in the general population.