Ahmed Salem, MD1, Sarah Meribout, MD1, Hazem Abosheaishaa, MD2, Mohammed Abusuliman, MD3, Neha Sharma, MD1, Mohamed Eldesouki, MD4, Omar Abdelhalim, MD5, Islam Mohamed, MD6, Fatima Khan, MD1, Syed Mujtaba Baqir, MD1, Samantha Ehrlich, MD1, Samar Pal S. Sandhu, MBBS1, Rajdeep Singh, MD7, Islam Rajab, MD8, Avleen Kaur, MD9, Abdallah Hussein, MD10, Carla Barberan Parraga, MD1, Nakul Mahajan, MBBS1, Mohammed Y. Youssef, MD11, Tanuj Chokshi, MD1, Joseph Menand, MD1, MariaLisa Itzoe, DO, MPH1, Bani Roland, MD12, Yuriy Tsirlin, MD1, Gerard Mullin, MD13, Mohammad Alomari, MD14, Sherif E. Elhanafi, MD15, Aaron Z. Tokayer, MD, MHS1 1Maimonides Medical Center, Brooklyn, NY; 2Mount Sinai West, Icahn School of Medicine at Mount Sinai, Queens, NY; 3Henry Ford Hospital, Detroit, MI; 4Saint Michael's Medical Center, New York Medical College, Newark, NJ; 5Icahn School of Medicine at Mount Sinai, Queens, NY; 6University of Missouri Columbia, Columbia, MO; 7PEACEHEALTH, Longview, WA; 8St. Joseph's University Medical Center, Paterson, NJ; 9SUNY Upstate Medical University, Syracuse, NY; 10Virtua Our Lady of Lourdes Hospital, Camden, NJ; 11Hunt Regional Medical Center, Greenville, TX; 12Brooklyn VA Medical Center, Brooklyn, NY; 13Johns Hopkins University School of Medicine, Baltimore, MD; 14University of Arkansas, Little Rock, AR; 15Texas Tech University Health Sciences Center, El Paso, TX Introduction:
Background: Colorectal cancer (CRC) incidence in adults under 50 has risen sharply, suggesting a shift in epidemiology. Identifying risk factors may improve early detection and guide screening efforts.
Aim: To identify clinical and metabolic predictors of early-onset colorectal cancer (EOCRC) in a real-world U.S. population. Methods: A retrospective case-control study was performed using TriNetX, a federated EHR database from 80+ U.S. healthcare institutions. Adults aged 30–49 with first-time CRC (ICD-10 C18–C20) between 2010–2023 were identified. Exclusions: prior malignancy, hereditary CRC syndromes (e.g., Lynch, FAP), inflammatory polyposis, or colectomy before diagnosis.
Each case was matched 1:2 to cancer-free controls based on age (±2 years), sex, and year of encounter. Predictors (within 2 years before diagnosis): obesity (E66), type 2 diabetes (E11), IBD (K50, K51), metabolic syndrome (E88.81), tobacco use (F17, Z72.0), physical inactivity (Z72.3), and family history of GI malignancy (Z80.0). Multivariable conditional logistic regression was used; AUC evaluated model performance. Multiple imputation addressed missing BMI and HbA1c data. Results: 3,217 EOCRC cases were matched with 6,434 controls (N=9,651). Mean age: 43.2; 52% male. EOCRC patients had higher prevalence of:
Obesity: 48.3% vs 29.1%
Diabetes: 32.5% vs 18.7%
Metabolic syndrome: 22.9% vs 12.8%
IBD: 9.7% vs 3.3%
Family history: 12.6% vs 5.1%
Inactivity: 18.4% vs 10.2% (all p< 0.01)
Independent predictors:
IBD: OR 2.43 (95% CI: 1.99–2.96)
Obesity: OR 2.08 (1.88–2.31)
Family history: OR 2.41 (2.02–2.87)
Metabolic syndrome: OR 1.77 (1.48–2.13)
Diabetes: OR 1.59 (1.36–1.85)
Smoking: OR 1.42 (1.22–1.67)
Model AUC was 0.81. Subgroup analysis revealed stronger associations in African American and Hispanic patients, and in those without prior CRC screening. Sensitivity analysis using Firth’s correction confirmed robustness. Discussion: EOCRC is associated with metabolic, inflammatory, and behavioral risk factors. These findings support EOCRC as a distinct entity and highlight the need for risk-based screening strategies for individuals under 50.
Figure: • Obesity, diabetes, metabolic syndrome, and IBD were significantly more common in EOCRC patients. • Family history and physical inactivity also strongly associated with EOCRC risk. • IBD and family history had the highest adjusted odds (OR ~2.4). • Final predictive model had AUC of 0.81, indicating strong discrimination. • Supports risk-based screening models for younger individuals under 50.
Disclosures: Ahmed Salem indicated no relevant financial relationships. Sarah Meribout indicated no relevant financial relationships. Hazem Abosheaishaa indicated no relevant financial relationships. Mohammed Abusuliman indicated no relevant financial relationships. Neha Sharma indicated no relevant financial relationships. Mohamed Eldesouki indicated no relevant financial relationships. Omar Abdelhalim indicated no relevant financial relationships. Islam Mohamed indicated no relevant financial relationships. Fatima Khan indicated no relevant financial relationships. Syed Mujtaba Baqir indicated no relevant financial relationships. Samantha Ehrlich indicated no relevant financial relationships. Samar Pal Sandhu indicated no relevant financial relationships. Rajdeep Singh indicated no relevant financial relationships. Islam Rajab indicated no relevant financial relationships. Avleen Kaur indicated no relevant financial relationships. Abdallah Hussein indicated no relevant financial relationships. Carla Barberan Parraga indicated no relevant financial relationships. Nakul Mahajan indicated no relevant financial relationships. Mohammed Y. Youssef indicated no relevant financial relationships. Tanuj Chokshi indicated no relevant financial relationships. Joseph Menand indicated no relevant financial relationships. MariaLisa Itzoe indicated no relevant financial relationships. Bani Roland indicated no relevant financial relationships. Yuriy Tsirlin indicated no relevant financial relationships. Gerard Mullin indicated no relevant financial relationships. Mohammad Alomari indicated no relevant financial relationships. Sherif Elhanafi indicated no relevant financial relationships. Aaron Tokayer indicated no relevant financial relationships.
Ahmed Salem, MD1, Sarah Meribout, MD1, Hazem Abosheaishaa, MD2, Mohammed Abusuliman, MD3, Neha Sharma, MD1, Mohamed Eldesouki, MD4, Omar Abdelhalim, MD5, Islam Mohamed, MD6, Fatima Khan, MD1, Syed Mujtaba Baqir, MD1, Samantha Ehrlich, MD1, Samar Pal S. Sandhu, MBBS1, Rajdeep Singh, MD7, Islam Rajab, MD8, Avleen Kaur, MD9, Abdallah Hussein, MD10, Carla Barberan Parraga, MD1, Nakul Mahajan, MBBS1, Mohammed Y. Youssef, MD11, Tanuj Chokshi, MD1, Joseph Menand, MD1, MariaLisa Itzoe, DO, MPH1, Bani Roland, MD12, Yuriy Tsirlin, MD1, Gerard Mullin, MD13, Mohammad Alomari, MD14, Sherif E. Elhanafi, MD15, Aaron Z. Tokayer, MD, MHS1. P4749 - Metabolic and Inflammatory Risk Factors for Early-Onset Colorectal Cancer: A US Case-Control Study, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
