Research Questions: Does frailty increase the risk of progression from inflammatory bowel disease (IBD) to colorectal cancer (CRC)? Which biological mechanisms mediate the relationship between frailty and the carcinogenic process in IBD? What is the genetic correlation and potential causal relationship between frailty and colorectal cancer?
Objectives: First, to assess the impact of frailty on the progression of IBD to CRC. Secondly, to investigate the mechanisms linking frailty to IBD-related carcinogenesis using data from the UK Biobank (UKB). Thirdly, to analyze the genetic correlation and establish potential causal links between frailty and CRC through Mendelian Randomization (MR).
Scientific rationale:
Global cancer statistics reveal nearly 20 million new cancer cases and 9.7 million cancer-related deaths in 2022. Frailty, a state of heightened vulnerability to stressors, has been linked to adverse health outcomes. Previous studies using UKB data have shown that frail individuals face a higher risk of developing cancer, with frailty identified as a predictor of cancers such as lung cancer.
IBD relapsing inflammation of the gastrointestinal tract due to an aberrant immune response to the gut microbiome. The prevalence of IBD exceeds 0.3% in many developed regions. A well-established association exists between IBD and CRC, UKB data reveal that IBD patients face an adjusted hazard ratio (HR) of 1.54 for CRC compared to the general population. The “inflammation-cancer transformation” model, originally proposed by Correa P. for gastric cancer. Similarly, IBD-associated CRC follows a pathway of “colonic inflammation!dysplasia!carcinoma”. Effective management of IBD is essential to improving patient outcomes and preventing this progression. Despite evidence suggesting that frailty influences cancer development, its role in the transition from IBD to CRC remains underexplored.
