colon cancer : Comment on the study by Ealey and Archer ( 2009 )

Dear Sir, It is now well known that obesity increases the risk of colon cancer and the risk is correlated with increased body mass index. Increased blood levels of leptin, insulin, IGF-1, IL-6 and TNF-a in obesity are considered to promote the carcinogenesis through activation of several intracellular signal pathways, including PI3K/Akt, MAPK and Stat3. Adiponectin counteracts these adverse effects, and thus decreased blood levels of adiponectin in obesity also contribute to the carcinogenesis of obesity-associated colon cancer. Knockout of the adiponectin gene and the adiponectin receptor genes 1 and 2 has been shown to accelerate azoxymethane (AOM)-induced colon cancer and this effect was alleviated by adiponectin supplement. We read with great interest the article by Ealey and Archer in your journal. To examine the role of adiponectin in the carcinogenesis of colon cancer, the authors developed mice with high levels of adiponectin expression and then fed them with a high-fat diet. The results showed that there is no difference in AOM-induced carcinogenesis between these and control mice. We believe that the experiment did indeed demonstrate that elevated adiponectin does not impart a preventative effect against AOM-induced colon cancer. However, the significance of the role of adiponectin in obesity-induced colon cancer risk cannot be excluded based on the results presented. This is because the high-fat diet is used in the later stages of the development of the disease and therefore may not play a key role in the development of colon cancer in the model. In the model developed by Ealey and Archer, a high-fat diet is provided 1 week after the final injection of AOM. However, it will take time for obesity to develop after feeding mice with a high-fat diet. In fact, adiponectin is initially increased after highfat feeding and levels decrease only after 10 weeks or later. Other factors may also change during the later stages of high-fat feeding. Lin et al. have developed a model of obesity by high-fat feeding, showing that obesity develops in 3 stages. Only in the third stage, the mice are resistant to leptin and have very high levels of insulin and leptin and low levels of adiponectin. This occurs after 15 weeks of feeding mice with a high-fat diet. At this time, AOM (a potent carcinogen)-induced colon cancer is well developed. Thus, the influence of obesity has limited significance in this model. In our opinion, the results of this experiment provide additional supportive evidence for the role of adiponectin in the prevention of obesity-induced colon cancer development. This is because adiponectin can block the risk factors for colon cancer that are associated with obesity, including increased insulin, leptin, IL-6 and TNF-a levels. Therefore, the challenge with AOM presented prior to obesity development was not affected by increased adiponectin expression; however, this is understandable. AOM causes colon cancer via DNA mutations. These mutations cause changed signal pathways including K-Ras, TNF-b and b-catenin. Adiponectin may not be very effective in preventing DNA mutations caused by AOM and changed signal pathways. In summary, the experiment demonstrated that adiponectin is not effective in the prevention of AOM-induced colon cancer prior to obesity development, but further study is needed to test whether adiponectin plays a preventive role in the obesityincreased risk of colon cancer.