Platelet-derived growth factor and risk factors for colorectal cancer

Platelet-derived growth factor (PDGF) is a potent mitogen for a variety of cells. Abnormal PDGF activity has been reported in many chronic diseases including cancer. Existing data suggest that fluctuations or reset homeostasis in normal growth factor production due to specific agents or changes in cellular environment are potential mechanisms of colonic carcinogenesis. Currently identified risk factors for colorectal cancer include diet, non-steroidal anti-inflammatory drug use, alcohol consumption and physical activity. Certain constituents of diet, including retinoids, fish oils and soybeans, inhibit the activity of PDGF and could reduce paracrine stimulation of the colonic epithelium. Aspirin and physical activity, through reduction in platelet aggregation, may inhibit platelet release of PDGF and lead to reset homeostasis. Alcohol affects platelet aggregation and, depending on consumption patterns, could alter platelet release of PDGF. It is important to determine which of these environmental factors may result in transient effects on growth factor activity and which result in long-term adaptive responses. Further studies could examine the impact of these risk factors on (1) growth factor communication between colonic epithelial cells and fibroblasts in vitro and (2) PDGF concentrations and mitogenic activity in blood and tissue obtained in population-based studies of colorectal cancer.