Fragile histidine triad (FHIT) gene, a candidate tumor suppressor gene located 
at 3p14.2, has been shown to be involved in carcinogenesis of many human 
tissues, including digestive tract tissues. However, the expression and role of 
FHIT in the initiation and the development of the colorectal cancer (CRC) are 
poorly understood. In our present study, we have demonstrated that the FHIT gene 
exhibits significantly decreased expression in human CRC compared to colorectal 
adenoma and normal colorectal tissue by tissue microarray (TMA). The positive of 
FHIT gene expression in normal colorectal tissue, adenoma and adenocarcinoma 
were 93.75%, 68.75% and 46.25%, respectively. We showed that decreased FHIT 
expression was significantly correlated with the progression of colorectal 
carcinoma (P<0.05) as well as differentiation and lymph node metastasis 
(P<0.05). Two somatic mutations in the FHIT gene were also detected in human 
CRC. The presence of these mutations correlated significantly with decreased 
FHIT expression in the human CRC. In addition, we identified decreased FHIT 
expression resulting in apoptosis inhibition and decreasing apoptosis associated 
with abnormal levels of some pro- and anti-apoptotic proteins (Bax, Bcl-2 and 
Survivin) by TUNEL and TMA. Our results demonstrated that the mutation in the 
FHIT gene significantly reduced FHIT expression in human CRC. Both TUNEL and TMA 
experiments demonstrated significantly inhibited apoptosis by down-regulation of 
Bax and up-regulation of Survivin and Bcl-2. Collectively, these studies 
identify the mechanism by which an important tumor suppressor gene, FHIT, 
inactivated specifically in human CRC, and contributes to our understanding of 
the mechanism of colorectal carcinogenesis.