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

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The model identified BMI, tobacco use, and family history of CRC as the strongest predictors for advanced neoplasia in young adults.

Carole Macaron, MD
Image courtesy of Cleveland Clinic

Carole Macaron, MD
Image courtesy of Cleveland Clinic

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

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