Risk of gastrointestinal malignancies and mechanisms of cancer development with obesity and its treatment.

Gastrointestinal malignancies may be associated with obesity, defined specifically by increased body-mass index, and based largely on environmental factors rather than genetics. In particular, there seems to be a definite increase in the incidence of both oesophageal and colorectal cancer. Mechanisms associated with obesity include a particular metabolic state characterized by hyperinsulinemia, or insulin resistance, along with elevated serum leptin. Leptin is derived from adipocytes and appears to play a role in the regulation of ghrelin, a peptide derived from the stomach and small intestine that stimulates appetite and weight gain. In addition to these metabolic changes, there are other anatomical alterations that may indirectly predispose to cancer, including the predisposition of obesity to gastroesophageal reflux and, possibly, oesophageal cancer. Other mechanisms may involve adipocyte-derived cytokines, or adipokines, that may serve as signalling devices in the pathogenesis of cancer. Finally, pharmacologic and surgical avenues available for treatment of obesity, including lipase inhibitors and gastric or jejuno-ileal bypass procedures may set the stage for subsequent gastric or intestinal tract cancer.