KI-RAS MUTATION MODIFIES THE PROTECTIVE EFFECT OF DIETARY MONOUNSATURATED FAT AND CALCIUM ON SPORADIC COLORECTAL-CANCER

The geographic differences in the incidence of colorectal cancer have been mostly attributed to variations in diet, The diversity of the Med iterranean diet and the heterogeneity of acquired genetic alterations in colorectal cancer sets the stage for investigating the possible ass ociation between dietary factors and mutations in tumor genes known to play a role in the pathogenesis of these neoplasms, With this purpose , we have studied the Ki-ras gene in 108 colorectal cancers using arch ival tissue and epidemiological data from our previous case-control st udy. Mutations in exon 1 of the Ki-ras gene were detected by a PCR-sin gle strand conformation polymorphism approach, A polychotomous logisti c regression model was used to assess the significance of observed dif ferences between wild-type and mutated tumors with respect to populati on controls in the different categories of nutrient consumption, Multi variate density models were used to adjust the correlation between nut rients and total energy. Our studies show that high consumption of mon ounsaturated fats, mostly derived from olive oil, is associated with a statistically significant decrease in the risk of cancer with wild-ty pe Ki-ras genotype but not of Ki-ms mutated cancers, Conversely, we fi nd that high calcium intake is associated with a decreased risk of Ki- ras mutated tumors but not of wild-type tumors, Tumor genotyping can r eveal epidemiological associations that are weak or unapparent when ca ses-control studies are not stratified by tumor genotype.