Association between gallstone disease and subsequent risk of sessile serrated adenoma/polyp (SSA/P).

• Applicant: Dr. Georgios Polychronidis
• Subject Area: Epidemiology and Medical Biometry/Statistics ; General and Visceral Surgery
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 426308975

Increasing evidence suggests that sessile serrated adenoma/polyp (SSA/P, which is different from conventional adenoma and develops over a different pathway) may be an important precursor lesion for proximal colon cancer. Given that the standard classification of these lesions has not been introduced until 2010, few aggravating factors and molecular pathways have been identified and further explored . Apart from lifestyle factors such as BMI and sugar intake, few other factors have been correlated to their development. The pathways from which they arise have not yet been explored, something which could facilitate screening and thus management of SSA/Ps. Compared to conventional adenomas that are characterized by chromosomal instability, the development of serrated lesions has been suggested to be driven by microsatellite instability (MSI). Based on the close relationship between MSI and inflammation, these lesions may be more strongly associated with the colon cancer-related inflammatory activities than conventional adenoma. A process which also has a strong connection with chronic inflammation is the development of gallstones. Gallstone disease (GD) arises mainly due to nutrition factors but also correlates with various others, while its presence has been vastly explored is various retrospective and prospective studies. In fact chronic inflammation is the growing ground for gallbladder cancer while a strong connection between GD and pancreatic cancer has also been shown. A number of cohort studies have associated right-side colon cancer with gallstone disease based only on the status post cholecystectomy but until recently only based on the cholecystectomy and not based on screening data. A correlation between GD and the risk for SSA/P has not yet been explored. This is a 24-month project entailing a cohort study analysis, a validation analysis and a case control study. The project will leverage data from both the Harvard cohort studies and the Partners Research Patient Data Registry (RPDR) to examine the link between the two gastrointestinal diseases and interrogate potential mechanisms through biomarker analysis. The findings will have important clinical implications for colorectal cancer prevention.

• DFG Programme: Research Fellowships
• International Connection: USA
• Hosts: Professor Albert Hofman, Ph.D.; Privatdozent Mingyang Song