ALTERED EICOSANOID LEVELS IN HUMAN COLON-CANCER

Eicosanoids may participate in colon carcinogenesis, as evidenced from work in animal tumor models showing prevention of colon cancer by inh ibitors of their synthesis and epidemiologic studies demonstrating red uced risk of colon cancer in long-term users of aspirin and other nons teroidal antiinflammatory drugs (NSAIDs). The levels of prostaglandin E2 (PGE2), PGF2alpha, PGI2, thromboxane A2 (TXA2), and leukotriene B4 (LTB4), which represent the cyclooxygenase and 5-lipoxygenase pathways , were determined in 21 pairs of surgically excised human colon cancer and histologically normal mucosa samples 5 to 10 cm away from the tum or. The levels of PGE2 were elevated in colon cancer samples as compar ed with histologically normal mucosa samples distant from the cancer ( p < 0.01), whereas levels of prostacyclin (PGI2)were decreased (p < 0. 05). The differences in the levels of PGF2alpha, TXA2, and LTB4 betwee n normal and malignant tissue were not statistically significant. No s tatistically significant association was found between the level of ea ch of the elcosanoids assayed and Dukes' stage of colon cancer. These findings, confirming and extending earlier work from tumors and cell c ulture, suggest that the protective effect of aspirin and other NSAIDs in the development of human colon cancer may be mediated, at least in part, through their inhibition of arachidonic acid metobolism by cycl ooxygenase.