DIET, HELICOBACTER-PYLORI, AND P53 MUTATIONS IN GASTRIC-CANCER - A MOLECULAR EPIDEMIOLOGY STUDY IN ITALY

A series of 105 gastric cancer (GC) cases with paraffin-embedded speci mens interviewed in a previous population-based case-control study con ducted in a highrisk area around Florence, Italy, was examined for the presence of p53 mutations, Overall, 33 of 105 cases had a mutation (p 53(+)) identified by single-strand conformational polymorphism and con firmed by sequencing (Y-H, Shiao ed at, submitted for publication), p5 3(+) cases had a more traditional dietary pattern (i.e., corn meal mus h, meat soup, and other homemade dishes) and reported less frequent co nsumption of raw vegetables (particularly lettuce and raw carrots), A positive association with a high nitrite intake and a negative associa tion with raw vegetables and diffuse type histology persisted in a mul tivariate analysis, In addition, p53(+) cases tended to be located in the upper portion of the stomach and to be associated with advanced ag e and blood group A, No relation was found between the presence of p53 mutations and histologically defined Helicobacter pylori infection, s moking history, family history of gastric cancer, education, and socia l class. Of the 33 p53(+) cases, 19 had G:C-->A:T transitions at CpG s ites, These tumors tended to occur in females and in association with H. pylori infection but not other risk factors, The remaining 14 cases with a p53 mutation had mainly transversions but also two deletions a nd two transitions at non-CpG sites, These tumors showed a strong posi tive association with a traditional dietary pattern and with the estim ated intake of selected nutrients (nitrite, protein, and fat, particul arly from animal sources), The findings of this ease-case analysis sug gest that p53 mutations at non-CpG sites are related to exposure to al kylating compounds from diet, whereas p53 mutations at CpG sites might be related to H. pylori infection.