The effect of body weight on altered expression of nuclear receptors and cyclooxygenase-2 in human colorectal cancers

Abstract

Background: Epidemiological studies on risk factors for colorectal cancer (CRC) have mainly focused on diet, and being overweight is now recognized to contribute significantly to CRC risk. Overweight and obesity are defined as an excess of adipose tissue mass and are associated with disorders in lipid metabolism. Peroxisome proliferator-activated receptors (PPARs) and retinoidactivated receptors (RARs and RXRs) are important modulators of lipid metabolism and cellular homeostasis. Alterations in expression and activity of these ligand-activated transcription factors might be involved in obesity-associated diseases, which include CRC. Cyclooxygenase-2 (COX-2) also plays a critical role in lipid metabolism and alterations in COX-2 expression have already been associated with unfavourable clinical outcomes in epithelial tumors. The objective of this study is to examine the hypothesis questioning the relationship between alterations in the expression of nuclear receptors and COX-2 and the weight status among male subjects with CRC.

The Anti-inflammatory Effect of Personalized Omega-3 Fatty Acid Dosing for Reducing Prostaglandin E2 in the Colonic Mucosa Is Attenuated in Obesity

“…Obesity induces COX-2 gene expression and stimulates COX-2 activity, thereby increasing PGE 2 concentrations in the human colon (15, 16). Endogenous synthesis of saturated fatty acids and mono-unsaturated fatty acids for storage is also favored under conditions of caloric excess (42).…”

“…The ideal tissue concentration of PGE 2 and other eicosanoids that allow for normal function without increasing cancer risk is yet to be determined. Nevertheless, there are important examples of abnormal regulation of PGE 2 in the histologically normal colon: expression of COX-1 in normal colonic mucosa of individuals at high risk for colon cancer was 2-fold higher than that in a normal risk group (13), high-fat diets induce COX-2 in colon of rodents (14), and obesity increases COX-2 expression in human colon (15, 16). Genetic polymorphisms of key enzymes in the pathways for synthesis, transport, and degradation of PGE 2 are also linked to risk of developing colorectal cancer (17, 18).…”

Obesity-associated cancer risk: the role of intestinal microbiota in the etiology of the host proinflammatory state

“…In another study, expression of cyclooxygenase-2, and inducible form of the enzyme, was higher in the colonic mucosa adjacent to tumor of obese versus normal weight subjects (58). …”

Esophageal COX-2 Expression Is Increased in Barrett’s Esophagus, Obesity, and Smoking

“…A case-control study from China investigating COX-2 polymorphisms in colorectal cancer found that in those with the COX-2 -765GG genotype, those with an overweight BMI had an OR of 3.91 (95 % CI 2.08-7.34) compared to those with a normal BMI, while the obese subjects had an OR of 2.03 (95 % CI 1.11-3.73) [19]. Another case-control study from France found that median COX-2 expression was higher in colorectal tumors from patients with BMI C 25 than from patients with BMI \ 25 (13.2 vs. 12.4; p value not provided) [20]. On the other hand, an experimental study in EA cell lines showed that leptin, an adiposederived hormone, stimulates cell proliferation and inhibits apoptosis in EA cells via activation of COX-2 [21].…”