Metabolomic profiling in relation to risks of cancer of the colon, rectum, pancreas, liver and biliary tract
We aim 1) to identify unique and shared metabolomic biomarkers for the risk of cancers of the colorectum, liver, pancreas and biliary tract; 2) to perform analyses to evaluate the inter-relationships of known lifestyle risk factors, blood metabolites, and cancer risk; 3) to evaluate genetic factors for these cancers and determine whether any genetic risk variants are also related to the metabolites identified in aim 1 for these cancers; and 4) to perform a genome-wide association study of blood metabolomics to better understand the inter-relationship of genetic factors, blood metabolites, and cancer risk of colorectum, pancreas, liver and biliary tract.
Globally, colorectal cancer is the third most commonly diagnosed cancer in males and the second most common in females. Pancreatic cancer is one of the most lethal malignant neoplasms in the world, and its five-year survival rate is only 9%. Liver cancer is the sixth most commonly diagnosed cancer and is the fourth leading cause of cancer death worldwide, while its incidence and mortality rates are two to three times higher among men. Biliary tract cancer is clinically heterogeneous and highly fatal. Approximately 90% of biliary tract cancer cases die within five years after diagnosis. However, the genetic factors affecting biliary tract cancer are poorly understood. These cancers all occur in the digestive system and share some etiologic factors. In particular, obesity and metabolic disturbances have been strongly implicated in the etiology of these cancers. We aim at identifying the unique and shared risk factors for these cancers, which will improve the understanding of their genetics, biology and etiology. The UK Biobank cohort provides an exceptional opportunity for this proposed study, which will generate valuable data for designing prevention strategies to reduce the incidence and mortality of these cancers.
Our group have extensive experience and established workflow to conduct genetic and biomarker analyses. Upon approval, we will work on this project for 24 months, including data analysis, manuscript preparation and presentation. Our previous studies provide strong evidence that metabolomic biomarkers exist in the circulation for colorectal cancer and pancreatic cancer. Our proposed study should be able to identify some biomarkers for cancers of the colorectum, liver, pancreas and biliary tract.