Approved research

The genetic basis of biliary tract cancers: a genome-wide, transcriptome-wide and phenome-wide association analysis

Lay summary

Biliary tract cancers are a clinically heterogeneous group of uncommon but highly lethal cancers including gallbladder cancer, cholangiocarcinoma, and ampulla of Vater cancer. The genetic basis of biliary tract cancers is poorly understood and no genetic factors have been identified for these cancers thus far mainly due to the small sample size and poor prognosis of the diseases, and the relative paucity of published studies. Thus, it is essential and urgent to pool and harmonize individual participant data from multiple small studies together to identify genetic factors for biliary tract cancers. Over the past several years, we have initiated the International Biliary Tract Cancer Consortium and collected approximately 6,600 cases with biliary tract cancer and 8,100 controls from multiple countries. The UK Biobank is a large prospective cohort study of approximately 500,000 subjects, including more than 500 cases with biliary tract cancer, with deep phenotypic and genetic data. In this project, we aim to comprehensively investigate the genetic basis of biliary tract cancers through a genome-wide, a transcriptome-wide and a phenome-wide association analysis using data from International Biliary Tract Cancer Consortium and UK Biobank. To address the issue, we propose to include the UK Biobank data as part of International Biliary Tract Cancer Consortium and perform the above-mentioned analyses regularly (i.e., once per year) in the next three years. We will start analyses as soon as data are available and plan to finish this project and send manuscripts to authors for review within 36 months after we receive the data. We hope that this study will facilitate our understanding of the genetic basis of biliary tract cancers and may help identify new biological pathways and therapeutic targets for improving prevention and treatment of these uncommon but highly lethal cancers.