The p53 gene in patients under the age of 40 with gastric cancer: mutationrates are low but are associated with a cardiac location

Background-Determining both the frequency and the spectrum of p53 gene muta tion in young patients with gastric cancer might provide clues to the host related genetic mechanism(s) in gastric carcinogenesis. Patients and methods-p53 mutations were assessed (by means of polymerase ch ain reaction-single strand conformation polymorphism (PCR-SSCP), followed b y DNA sequencing) in a cohort of 105 consecutive Italian patients in whom g astric cancer was ascertained before the age of 41. Results-A low prevalence of p53 mutations (eight of 105) was observed, with no significant difference between intestinal (three of 31; 10%) and diffus e (five of 74; 7%) phenotypes. A significantly higher prevalence of p53 mut ations was associated with the cardiac location (odds ratio, 7.09; confiden ce interval, 1.56 to 32.11). In all but one case, p53 mutations were associ ated with a stage higher than I. All eight mutations were located at CpG si tes, where G : C to A: T transitions have been associated with frequent met hylation at the C5 position of cytosine. Conclusions-These findings show that, unlike what has been consistently dem onstrated in the general population, p53 mutations are uncommon in gastric cancer occurring in young patients, and in such patients, p53 alterations a re significantly associated with the cardiac location.