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Introduction
Colorectal cancer (CRC) is a malignant neoplasm arising from the lining of the large intestine (colon and rectum). CRC is the third most common malignancy and one of the major causes of cancer-related death in the United States (1). Colitis-associated cancer (CAC) is the type of colon cancer which is preceded by clinically detectable inflammatory bowel disease (IBD), such as Crohn’s disease (CD) or ulcerative colitis (UC) (2). IBD results from the inappropriate and ongoing activation of the mucosal immune system, and this is driven by the presence of normal luminal flora. As many as 1.4 million persons in the United States and 2.2 million persons in Europe suffer from these diseases (3). The incidence of IBD in Korea has increased significantly over the past few decades. In case of prevalence for UC in South Korea, it was quadrupled from 7.57/105 individuals in 1997 to 30.9/105 individuals in 2005. Adjusted prevalence rates of CD and UC per 105 individuals were 11.2 and 30.9, respectively (4). In case of incidence of IBD in Japan, the number of patient is increased with time. The age-standardized prevalence of UC in Japan in 2005 was 63.6/105 individuals, and that of CD was 21.2/105 individuals. Incidence rate of UC and CD are higher than South Korea. The prevalence of inflammatory bowel diseases is much lower in Asian countries, including Japan and Korea, than in Western countries, but it is rapidly increasing (5). Chronic IBD such as UC and CD cause colitis-associated colon cancer.
Peroxisome proliferator-activated receptors γ (PPARγ), which belongs to the nuclear receptor superfamily, is a ligand-activated transcription factor that forms heterodimer with retinoic X receptor (RXR) and stimulates expression of target genes. It is expressed in various tissues and cell types, including those from the pancreas, liver, kidney, adipose tissue and colon (6). Further, several lines of evidence indicate that PPARγ plays an important role in regulating inflammatory responses in the intestine (7). PPARγ and its activators are known as important modulators having anti-inflammatory properties that can modulate nuclear factor-κB (NF-κB) activation. Rosiglitazone, PPARγ activator, was tested in clinical trials and was found to be effective in the treatment of UC (8). Dietary punicic acid ameliorates intestinal inflammation by activation of PPARγ...