S613 Non-Genetic Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis

Introduction: Early-onset colorectal cancer (EOCRC), defined as colorectal cancer (CRC) diagnosed before age 50, is increasingly prevalent and has become a leading cause of cancer-related death among younger adults worldwide. We aimed to comprehensively identify non-genetic risk factors associated with EOCRC. Methods: We conducted a systematic review and meta-analysis of observational studies that evaluated non-genetic EOCRC risk factors in individuals aged <55 years. PubMed, EMBASE, Scopus, and the Cochrane Library were searched through November 2024. Manuscripts and abstracts published in English were included. We performed random-effects meta-analyses and evaluated heterogeneity and publication bias. Study quality was assessed using the Newcastle-Ottawa Scale. We conducted sensitivity analyses excluding abstracts, low-quality studies, studies with participants outside the ages of 18-49, and studies that adjusted for less than 2 variables. Results: We screened 4224 studies, of which 91 were included in the systematic review and 79 were eligible for meta-analysis. The analysis included data from over 300,000 EOCRC cases. Significant risk factors included demographic (family history of polyps and cancer, White race, unemployment), comorbidity (chronic kidney disease, inflammatory bowel disease, obesity, diabetes, hypertension, hyperglycemia, metabolic syndrome, abdominal obesity, non-alcoholic fatty liver disease, weight gain since age 18-20), and lifestyle/exposure (sugary beverages, fried food, sweet food, processed meat, alcohol, smoking, red meat) risk factors. Protective factors were calcium, higher education, statins, vitamin D, and vitamin supplementation. In sensitivity analyses, Asian race, no aspirin use, no nonsteroidal anti-inflammatory drug use, and sedentary lifestyle became significant; calcium, education, red meat, processed meat, and weight gain became nonsignificant. Heterogeneity was high among variables with at least 5 studies, except for metabolic syndrome (I2 = 0.0). Most variables did not have evidence of publication bias. Conclusion: This study confirms known EOCRC risk factors and identifies additional risk factors that warrant further investigation. These findings provide a foundation for improving EOCRC risk assessment and developing targeted screening strategies to facilitate early detection in high-risk populations.