The interaction effects of genetic susceptibility and biliary tract diseases and the incidence of gastrointestinal cancer
Recently, there is increasing interests to generate polygenic scores by combining these single-nucleotide polymorphisms (SNPs) to reveal the overall effect of genetic architecture on common diseases, such as body mass index (BMI)-related polygenic scores in association with cardiovascular disease, diabetes mellitus, and obesity-related cancers (e.g. hepatocarcinoma, pancreatic cancer, colorectal cancer, etc.). The effect of these metabolism-related SNPs in gastrointestinal cancers is unknown. To our knowledge, few studies have paid attention to the interaction between biliary tract diseases and genetic susceptibility in the development of gastrointestinal cancers. In this study, we will construct polygenic scores for SNPs and analyze polygenic scores modify the effects of biliary tract diseases on the occurrence of gastrointestinal cancers. The extent of the metabolomics signatures in mediating the associations between biliary tract diseases, SNP scores, and metabolic diseases will further be explored.
A combination of PRS, environmental factors and clinical factors had shown good performance in identification of high-risk populations for breast cancer and prostate cancer.Therefore, we will construct a PRS for gastrointestinal cancers, and evaluate its effectiveness in the UK Biobank as well as the PLCO cohort study respectively. At last, we plan to develop a gastrointestinal cancer risk prediction model based on the PRS, metabolites and history of biliary tract diseases based on the UK Biobank, and evaluated its application value in the PLCO cohort .
Our study will help to promote the understanding of gastrointestinal cancers, and the model could be used in identifying groups of individuals who are at high risk of severe gastrointestinal cancers and more likely to benefit from interventions.
This project aims to:
(i) Unravel the interaction effect of biliary tract diseases on the development of gastrointestinal cancer including biliary cancer, colorectal cancer, pancreas cancer, upper GI caner and liver cancer;
(ii) Identify biliary tract diseases or genetic susceptibility-related metabolomics signatures, and investigate their association with gastrointestinal cancer;
(iii) Reveal the risk prediction ability of the identified signatures for gastrointestinal cancer risk and related mortality.
Hongbing Shen, Professor of Epidemiology, Nanjing Medical University
Meng Zhu, Professor of Epidemiology, Nanjing Medical University