Aberrant FHIT Expression Linkage to Bladder Carcinogenesis and Apoptosis

The bladder is a common site for cancer development in the urinary tract. Urinary bladder cancer ranks ninth in worldwide cancer incidence; it is the seventh most common malignancy in men and 17th in women. In the United States and Western Europe, the lifetime risk is about 1 in 25 and 1 in 80 for white males and females, respectively. Furthermore, approximately 145,000 patients die from this disease worldwide per year (Greenlee et al., 2000; Parkin, 2008; Ploeg et al., 2009). Majority of bladder tumors originate from transitional epithelium or urothelium, a multi-layered epithelium without squamous cells, which covers the inside of this organ (Naik et al., 2011). Fragile Histidine Triad (FHIT) gene is located at 3p14.2 (Ohta et al., 1996) and its gene product, FHIT protein, is a diadenosine triphosphate (Ap3A) hydrolase belonging to the histidine triad superfamily of nucleotidebinding proteins (Huang et al., 1995; Barnes et al., 1996). FHIT is a tumor suppressor gene vital to the maintenance of proper cell growth and division. Although the exact mechanism of tumor suppression by FHIT remains unclear, it is apparent that in its absence, cell cycle homeostasis is often perturbed resulting in the development of soft tissue tumors. First identified in digestive tract cancers,