A functional polymorphism within the distal promoter of RUNX3 confers risk of colorectal cancer

Abstract

Background Accumulating evidence has indicated that runt-related transcription factor 3 ( RUNX3) gene polymorphism (rs7528484) is associated with an alimentary system cancer risk. However, the role of rs7528484 in colorectal cancer is still unclear. The present study aimed to explore the association between rs7528484 and colorectal cancer susceptibility in a Chinese Han population. Material and methods We firstly investigated the effect of the polymorphism rs7528484 in distal promoter of RUNX3 polymorphism on colorectal cancer risk in a Chinese Han population comprising 427 colorectal cancer patients and 503 controls. We then carried out a phenotype–genotype association analysis to validate its influence on the adjacent gene RUNX3. Results Logistic regression analysis demonstrated that the T allele of rs7528484 was significantly associated with an increased risk for colorectal cancer occurrence in our case-control study (odds ratio = 1.33; 95% confidence interval = 1.09–1.65; P = 0.005). In stratified analysis, the susceptibility of colorectal cancer in the T allele carriers increased among the smokers, III and IV tumor stage, and at the rectum. Furthermore, the T allele was significantly correlated with lower expression of RUNX3 in vitro. Conclusion In summary, the current case-control and genotype–phenotype study provides convincing evidence that functional RUNX3 polymorphism (rs7528484) is related to colorectal cancer risk and is a plausible marker for the prediction of colorectal cancer.

High Expression of IRS-1, RUNX3 and SMAD4 Are Positive Prognostic Factors in Stage I–III Colon Cancer

“…They are directly involved in important signaling pathways including the ERK, PI3K/AKT, TGF-β pathways, among others [7][8][9][10]. Moreover, they are already implicated in colon cancer development through cell line experiments and a few prognostic studies [11][12][13]. IRSs are important in insulin signaling and maintain cellular functions such as growth, survival, and metabolism [14].…”