p53 over-expression and p53 mutations in colon carcinomas: Relation to dietary risk factors

Epidemiological studies have suggested that dietary factors may differently affect p53-dependent and p53-independent pathways to colon cancer. Results of such studies may depend on the method used to assess p53 status. This c ase-control study of 185 colon-cancer cases and 259 controls examiner this relation, using both immunohistochemistry and SSCP(exons 5-8)/sequencing to detect p53 abnormalities. Of 185 carcinomas analyzed using immunohistochem istry, 81 (44%) were categorized as p53 over-expression. p53 mutations were detected in 59 tumors (32%). A slight increase in risk observed for intake of saturated fat was largely due to an increased risk in cases without p53 over-expression (OR per 16.1 g/day, 1.46; 95% CI, 1.08-1.97), and no assoc iation in cases with p53 over-expression (OR, 1.07, 95% CI, 0.78-1.47). How ever, findings were less pronounced when cases were classified by mutation analysis (wild-type OR, 1.33; 95% CI, 1.01-1.75; mutated OR, 1.16; 95% CI, 0.81-1.65). Similar results were observed for total fat intake. For other n utrients and fdr vegetable and meat food groups no differences in risk for either p53 pathway were observed, independent of the laboratory technique u sed. Interestingly, in cases with transversion mutations in the p53 gene, a n increased risk was observed for saturated fat (OR, 2.00; 95% CI, 0.97-4.1 4), in contrast to those with mutations at CpG sites (OR, 0.93; 95% CI, 0.5 5-1.57). An increase in colon-cancer risk for the p53-independent pathway d ue to fat intake, is more pronounced when using immunohistochemistry. Howev er, mutation analysis is needed to study the possible association with a sm all group of tumors with transversion mutations. (C) 1999 Wiley-Liss, Inc.