AIM:To evaluate the role of N-myc downstreamregulated gene 1 (NDRG1) expression in prognosis and survival of colorectal cancer patients with different ethnic backgrounds.METHODS: Because NDRG1 is a downstream target of p53 and hypoxia inducible factor-1α (HIF-1α), we examined NDRG1 expression together with p53 and HIF1α by immunohistochemistry. A total of 157 colorectal cancer specimens including 80 from Japanese patients and 77 from US patients were examined. The correlation between protein expression with clinicopathological features and survival after surgery was analyzed.RESULTS: NDRG1 protein was significantly increased in colorectal tumor compared with normal epithelium in both Japanese and US patient groups. Expression of NDRG1 protein was significantly correlated with lymphatic invasion, venous invasion, depth of invasion,histopathological type, and Dukes'stage in Japanese colorectal cancer patients. NDRG1 expression was correlated to histopathological type, Dukes'stage and HIF-1α expression in US-Caucasian patients but not in US-African American patients. Interestingly, Kaplan-Meier survival analysis demonstrated that NDRG1 expression correlated significantly with poorer survival in US-African American patients but not in other patient groups.However, in p53-positive US cases, NDRG1 positivity correlated significantly with better survival. In addition,NDRG1 expression also correlated significantly with improved survival in US patients with stages Ⅲ and Ⅳtumors without chemotherapy. In Japanese patients with stages Ⅱ and Ⅲ tumors, strong NDRG1 staining in p53-positive tumors correlated significantly with improved survival but negatively in patients without chemotherapy.CONCLUSION: NDRG1 expression was correlated with various clinicopathological features and clinical outcomes in colorectal cancer depending on the race/ethnicity of the patients. NDRG1 may serve as a biological basis for the disparity of clinical outcomes of colorectal cancer patients with different ethnic backgrounds.