S547 Modifiable Determinants of Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis

Introduction: Despite an overall decline in the incidence of colorectal cancer (CRC) in the last few decades, the incidence of CRC in younger adults (<50 years), early-onset CRC (EOCRC), is on the rise. Several risk factors have been described as linked with EOCRC. With poorer survival outcomes associated with EOCRC, it is essential to explore all the modifiable risk factors impacting the incidence of EOCRC. Methods: We conducted a comprehensive literature search using PubMed, Embase, and Google Scholar, from inception through February 2025, to identify all the published studies analyzing any risk and protective factors for EOCRC. We included observational studies that were either limited to EOCRC cases or provided age-stratified incidence and compared the incidence to disease-free or risk-free controls. Two independent reviewers screened titles, abstracts, and full texts. Random-effects meta-analyses were performed to pool effect estimates, and heterogeneity was quantified using the I² statistic. Results: From 1,209 initial citations, a total of 49 studies were included. Significant risk factors for EOCRC were chronic comorbidities, including diabetes mellitus [odds ratio [OR] = 1.97 (1.06-3.69)], hypertension [OR = 1.61 (1.08-2.41)], obesity [OR = 1.52 (1.10-2.10)], lifestyle factors including tobacco smoking [OR = 1.33 (1.05-1.68)], alcohol consumption [OR = 1.35 (1.00-1.81)], and antibiotic use, both anti-anerobic [OR = 1.33 (1.00-1.77)] and anti-aerobic [OR = 1.33 (1.02-1.72)]. Metabolic syndrome (OR = 1.28), hyperlipidemia (OR = 1.31), and red meat consumption (OR = 1.28) increased the risk but did not reach significance. Having good physical activity was the only protective factor that reached statistical significance [OR = 0.68 (0.51-0.92)]. Vitamin D intake (OR = 0.76), vegetable consumption (OR = 0.87) reduced the risk non-significantly, and aspirin intake (OR = 0.99) and fish consumption (OR = 0.99) played no role. Conclusion: Our study identifies and quantifies the modifiable factors influencing the incidence of EOCRC. With the rising incidence and poorer outcomes of EOCRC, it is vital to recognize and direct interventions towards the at-risk populations.