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ABSTRACT Epidemiologic studies of breast and pancreatic cancer in several Mediterranean populations have demonstrated that increased dietary intake of olive oil is associated with a small decreased risk, or no increased risk, of cancer, despite a high overall lipid intake. Experimental animal models in high dietary fat and cancer also indicate that olive oil either has no effect, or a protective effect, on the prevention of a variety of chemically induced tumors. As a working hypothesis, it is proposed that the high squalene content of olive oil, as compared to other human foods, is a major factor in the cancer-risk reducing effect of olive oil. Experiments in animal models suggest a tumor-inhibiting role for squalene. A mechanism is proposed for the tumor-inhibitory activity of squalene based on its known strong inhibitory activity of HMG-COA reductase catalytic activity in vivo, thus reducing farnesyl pyrophosphate (FPP) availability for “prenylation” of ras oncogene, which relocates this oncogene to cell membranes and is required for the signal-transducing function of ras. Reduction of mutated ras oncogene activation may be useful in breast and colon cancer and may be particularly applicable to pancreatic cancers that are strongly associated with ras oncogenes.