EXPLORING THE CAUSAL RELATIONSHIPS BETWEEN APPENDICITIS, APPENDECTOMY, AND COLORECTAL CANCER: IMPLICATIONS FOR PHYSICAL ACTIVITY AND LONG-TERM HEALTH OUTCOMES

Abstract

Background: The relationship between appendicitis or appendectomy and colorectal cancer (CRC) has long been debated in clinical and epidemiological research. This study aimed to determine the potential causal association between these conditions through Mendelian randomization (MR) analysis, offering insights relevant to long-term health outcomes and physical activity participation after gastrointestinal surgeries. Methods: Genome-wide association study (GWAS) data from individuals of European descent were obtained from the IEU OPEN GWAS PROJECT and FinnGen. Relevant single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) based on the core assumptions of MR analysis. The inverse variance weighted (IVW) method was used to examine potential causal links between appendicitis or appendectomy and CRC risk. To strengthen reliability, findings were cross-validated using an independent dataset, with additional stratification of CRC cases by anatomical site into colon and rectal cancer subtypes. Results: The IVW-based MR analysis revealed no significant causal associations between appendicitis, appendectomy, and CRC. Reverse MR analysis similarly indicated no evidence of CRC causing appendicitis. Subgroup analysis based on anatomical sites (colon or rectal cancer) confirmed the absence of any causal relationships. Conclusions: The findings from this MR analysis provide robust evidence against a causal link between appendicitis or appendectomy and CRC development. These results support current clinical practices and encourage further research into modifiable lifestyle factors, including physical activity and exercise regimens, as potential protective strategies against CRC, particularly for post-surgical patients in sports and medical rehabilitation contexts.