Gamal Othman Dabwan
Background Colorectal cancer (CRC) forms a serious health challenge in developed countries. In Yemen, khat ( Catha edulis ) chewing and smoking represent a common health risk, raising the risk of insulin resistance and potentially stimulating malignant tumors. However, studies of the DIP2 family, especially DIP2C , are virtually absent in the Middle East, notably in Yemen, so this study focused on serum DIP2C levels in the context of colorectal cancer and khat chewing and smoking habits. Objective This study aimed to investigate the serum DIP2C protein levels in CRC patients and to evaluate the influence of malignant patterns, age, BMI, smoking, and khat chewing on its concentration. Methods In this study, 214 Yemeni adults aged 20–90 years were enrolled, including 73 CRC patients (25 with MetS and 48 without MetS) and 141 non-cancerous individuals (70 non-CRC, non-MetS subjects served as controls, and 71 non-CRC, MetS subjects). DIP2C levels were evaluated in relation to tumor risk factors, including age, body mass index (BMI), smoking, and khat use. Diagnostic performance was evaluated using ROC analysis. Results Serum DIP2C levels were significantly lower in CRC patients with and without MetS compared to control individuals ( P = 1.5×10– 7 and 0.043 ). No significant differences in DIP2C levels were observed across subgroups stratified by MetS status, age, BMI, smoking status, or khat chewing status among non-CRC participants. ROC analysis demonstrated moderate discriminative performance, with an AUC of 0.755 (95% CI: 0.686–0.823), a sensitivity of 80.8%, and a specificity of 60.3%. Conclusion Yemeni patients with colorectal cancer have noticeably low serum DIP2C protein levels with a sensitivity of 80.8%, a specificity of 60.3%, and a cut-off of 0.425. However, further functional studies are necessary to fully understand the potential of serum Dip2C as a biomarker for colorectal cancer (CRC) and its use as a diagnostic test for CRC.