Approved research

Causes of biliary tract cancers: evidence from prospective observational studies, genome-wide association analysis and mendelian randomization

Lay summary

Biliary tract cancers are a clinically heterogeneous group of uncommon cancers including gallbladder cancer, cholangiocarcinoma, and ampulla of Vater cancer. The pathogenesis of these highly lethal cancers is poorly understood. To date, only a few environmental and genetic factors have been identified to be associated with biliary tract cancers. Furthermore, environmental factors such as gallstones are strongly associated with biliary tract cancers, particularly one of the specific subtypes, but whether these associations are causal remains unclear. This question has clinical significance since prevention or early treatment of gallstones may ultimately reduce the incidence of biliary tract cancers. In this project, we aim to systematically investigate environmental and genetic factors of biliary tract cancers, and examine whether risk factors identified in prospective observational studies such as gallstones, cholecystitis and obesity are causally associated with risk of biliary tract cancers. To address these issues, we will conduct a meta-analysis of prospective observational studies, a genome-wide association study and a mendelian randomization analysis using data from UK Biobank and other sources. We will start analyses as soon as data are available and plan to finish this project and send manuscripts to authors for review within 18 months after we receive the data. We hope that this study will provide summary data for the relationships between environmental and genetic factors and risk of biliary tract cancers, and advance our understanding of the etiology of these uncommon but highly lethal cancers. Our study is consistent with the goal of UK Biobank that dedicates to improve the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses like biliary tract cancers.