Principal Investigator: Professor Ben Zhang
First Affiliated Hospital Army Medical University, ChinaTags: 45902, Biliary tract cancer, cause, epidemiology, genome-wide association, Mendelian randomization, risk factor
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.
Project extension February 2019:
Biliary tract cancers represent a clinically heterogeneous group of uncommon cancers that arise in the gallbladder, bile ducts and ampulla of Vater. Gallbladder cancer and cholangiocarcinoma are two major subtypes of biliary tract cancer while ampulla of Vater cancer only accounts for a very small fraction of biliary tract cancer. Typically, gallbladder cancer affects women more frequently than men and cholangiocarcinoma is more common in men than women, suggesting that there may be gender specific risk factors for biliary tract cancers. Thus, we propose to extend our project and perform additional analyses to investigate gender specific causes of biliary tract cancers based on the initial application using data from UK Biobank, International Biliary Tract Cancer Consortium, and other sources. Specifically, we will first evaluate the heritability of gallbladder cancer, cholangiocarcinoma, and ampulla of Vater cancer in men and women. Second, we will investigate gender specific environmental exposures, genetic factors, and gene-environment interactions for gallbladder cancer, cholangiocarcinoma, and ampulla of Vater cancer. Third, we will conduct a mendelian randomization analysis to examine whether the gender specific environmental factors are causally associated with subtypes of biliary tract cancer. All these analyses are consistent with the study scope in the initial application and will facilitate to further understand the etiology of biliary tract cancers.
Last updated Mar 12, 2019