Cleveland Clinic Researchers Develop Risk-Prediction Model for Early-Onset Colorectal Cancer in Young Adults

Researchers at Cleveland Clinic have developed and internally validated a risk-prediction model to estimate the likelihood of advanced colorectal neoplasia in adults younger than 45 years. The findings were published in Digestive Diseases and Sciences.¹

While colorectal cancer (CRC) incidence has declined overall due to screening, early-onset CRC is on the rise, particularly in individuals younger than 45 years — an age group not currently recommended for CRC screening, according to investigators.¹

“Currently, for individuals at average risk of developing colorectal cancer, the recommended age to start screening is 45 years old,” lead author Carole Macaron, MD, a gastroenterologist at Cleveland Clinic, said in a press release.² “However, data show that about half of the patients diagnosed with early-onset colorectal cancer are younger than 45.”

Studies have shown that the risk for early-onset advanced neoplasia varies based on several factors, including sex, race, family history of CRC, smoking, alcohol consumption, diabetes, hyperlipidemia, obesity, and diet. A score that incorporates some of these factors to identify which younger adults are at higher risk for advanced neoplasia, a precursor to CRC, could support earlier, more targeted screening interventions, researchers explained.¹

To develop and validate their risk score, Macaron and colleagues conducted a retrospective cross-sectional analysis of 9446 people aged 18-44 years (mean age, 36.8 years; 61% women) who underwent colonoscopy at their center between 2011 and 2021. Advanced neoplasia was defined as a tubular adenoma ≥ 10 mm or any adenoma with villous features or high-grade dysplasia, sessile serrated polyp ≥ 10 mm, sessile serrated polyp with dysplasia, traditional serrated adenoma, or invasive adenocarcinoma.¹

The 346 (3.7%) individuals found to have advanced neoplasia served as the case group, and the remainder with normal colonoscopy or non-advanced neoplasia served as controls. A multivariate logistic regression model identified 3 independent risk factors significantly associated with advanced neoplasia: Higher body mass index (BMI; P = .0157), former and current tobacco use (P = .0009 and P = .0015, respectively), and having a first-degree relative with CRC < 60 years (P < .0001) or other family history of CRC (P = .0117).¹

Macaron and her team used these risk factors to develop a risk prediction score to estimate the likelihood of detecting advanced neoplasia, which ranged from a risk of 1.8% for patients with a score of 1 to 22.2% for those with a score of 12. Individuals with a score of ≥9 had a risk of 14% or more for advanced neoplasia and were recommended for screening.¹

The model demonstrated “moderate” discriminatory power in the validation set (C-statistic: 0.645), indicating that it can effectively differentiate between individuals at a higher and lower risk for advanced neoplasia.¹

“We developed and internally validated a simple score using clinical factors which successfully predicts the likelihood of AN in adults < 45 years undergoing colonoscopy. Once externally validated, the proposed risk score may be useful for individualized CRC screening strategies,” investigators concluded.¹

References:

1. Macaron C, Wehbe S, Liska D, et al. A score to predict advanced colorectal neoplasia in adults younger than age 45. Dig Dis Sci. Published online February 13, 2025. doi:10.1007/s10620-025-08861-y

2. Cleveland Clinic Develops Prediction Score to Estimate Risk of Early-Onset Colorectal Cancer and Precancerous Polyps. News release. Cleveland Clinic. March 3, 2025. Accessed March 28, 2025. https://newsroom.clevelandclinic.org/2025/03/03/cleveland-clinic-develops-prediction-score-to-estimate-risk-of-early-onset-colorectal-cancer-and-precancerous-polyps