大腸直腸癌是全球第三常見的癌症，同時在全球癌症相關死因排名第二，而且大腸直腸癌發生率有逐年上升的趨勢。在台灣，大腸直腸癌的發生率分別高居男性與女性的第一位和第二位，死亡率則是總體癌症的第三位。提供適當的大腸直腸癌篩檢可以早期發現、早期治療、改善預後，進而降低總體醫療成本。
根據「腺瘤-癌」形成理論，大腸直腸癌的發生需要10年甚至更久的時間，才能從正常的腸道黏膜長出腺瘤，最終發展成癌症。雖然目前大多數的篩檢準則建議一般風險族群從年滿50歲開始接受篩檢，但近年發現大腸直腸癌的發生有年輕化的趨勢，因此新公布的準則也將45-49歲一般風險族群列入篩檢目標。
本研究收集2018年1月1日至2022年9月21日於國立成功大學醫學院附設醫院健康管理中心年齡未滿50歲且首次接受大腸鏡檢查的受檢者，排除不符合條件的受檢者後，共3,439人納入分析。資料經整理並刪除與研究結果無關且缺失值過高的變項後，將樣本隨機分為訓練組（2,751人，80%）與驗證組（688人，20%），並分別進行50次多重插補。本研究針對三種結果：所有腺瘤與高風險情境：包含高風險腺瘤與進階性腺瘤建構預測模型。所有模型皆顯示年齡、抽菸、代謝性脂肪肝病（進階性腺瘤再加上後續的丙胺酸轉胺酶偏高）為顯著風險因子。男性僅在腺瘤模型中為顯著風險因子，顯示其可能與病灶早期形成比較有相關性。鑑別度與校準度分析除了腺瘤模型鑑別度較差（AUC = 0.703）外，高風險情境的模型皆顯示為中等的鑑別度（AUC = 0.774-0.760），且有良好的校準表現，Brier Score為0.025-0.138，Calibration slope大約等於1，E/O ratio大約等於1，Calibration-in-the-large大約等於0。建立起的評分系統雖然會讓鑑別度稍微下降，且陽性預測率受到原本盛行率不高的影響因此偏低（9.14%-27.38%），但有不錯的陰性預測率（90.43%-98.23%）
驗證分析顯示高風險腺瘤具備中等的鑑別與預測能力（AUC= 0.76，Brier Score = 0.040），進階性腺瘤則稍差（AUC= 0.746，Brier Score = 0.029），而腺瘤模型則表現較差。三個模型在驗證組中皆顯示良好之校準表現（Calibration slope大約等於1，E/O ratio大約等於1，Calibration-in-the-large大約等於0）。將建立起的評分系統帶入驗證組資料驗證雖然顯示較差的模型鑑別度（0.648-0.685），但其陰性預測率維持高水準（90.34%-97.82%），可做為臨床判斷排除低風險個體方面具有良好表現。因此模型應可作為有效的風險分層與篩檢輔助工具，協助臨床上辨識可暫緩大腸鏡檢查之低風險族群。總結來說，年齡、抽菸、代謝性脂肪肝病（進階性腺瘤再加上後續的丙胺酸轉胺酶偏高）為早發型腺瘤下所有情境的共同風險因子，男性僅在低風險情境中為顯著風險因子。本研究建立起的評分系統可作為辨識可暫緩大腸鏡檢查之低風險族群之用。

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer-related mortality. Although most screening guidelines recommend initiating CRC screening at age 50 for average-risk individuals, the incidence of early-onset CRC has increased, prompting recent guideline updates to include individuals aged 45-49 years. However, risk stratification tools for younger populations remain limited.
This study aimed to identify clinical risk factors and develop predictive models for early-onset colorectal neoplastic lesions in individuals younger than 50 years, a population in whom colorectal cancer incidence has been increasing and for whom optimal screening strategies remain uncertain.
We conducted a retrospective study including individuals younger than 50 years who underwent their first colonoscopy at the Health Management Center of National Cheng Kung University Hospital between January 1, 2018, and September 21, 2022. After exclusions, 3,439 participants were included. The dataset was randomly divided into a training group (80%, n = 2,751) and a validation group (20%, n = 688), with 50 rounds of multiple imputation performed in each set. Predictive models were developed for three outcomes: adenoma, high-risk adenoma, and advanced adenoma.
Across all models, age, smoking status, and metabolic dysfunction–associated fatty liver disease (MAFLD) were consistently identified as significant risk factors, with elevated alanine aminotransferase additionally associated with advanced adenoma. Male sex was a significant risk factor only in the adenoma model, suggesting a role in early lesion development. In the training set, the adenoma model showed limited discrimination (AUC = 0.703), whereas the high-risk and advanced adenoma models demonstrated moderate discrimination (AUC = 0.774-0.760) and good calibration. All models showed favorable calibration metrics, including calibration slopes near 1 and expected-to-observed ratios close to 1.
Risk scoring systems were derived from regression coefficients. Although discrimination decreased after score transformation and positive predictive values were low due to the low prevalence of outcomes (9.14%-27.38%), negative predictive values remained high (90.43%-98.23%). In validation analyses, the high-risk adenoma model retained moderate predictive performance (AUC = 0.76), while the advanced adenoma model performed slightly less well (AUC = 0.746); all models maintained good calibration. When applied as scoring systems in the validation set, discrimination was reduced (AUC = 0.648-0.685), but negative predictive values remained high (90.34%-97.82%).
In conclusion, age, smoking, and MAFLD are common risk factors for early-onset adenomas across different risk levels, while male sex appears to be associated primarily with early lesion formation. The proposed risk scoring systems, despite moderate discrimination, demonstrate strong ability to exclude low-risk individuals and may serve as practical tools for risk stratification and prioritization of colonoscopy in younger populations.

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