Alterations in exon 4 of the p53 gene in gastric carcinoma

Background & Aims: Our long-term goal was to evaluate the role of p53 in th e prognosis of gastric cancer. We previously showed a discrepancy between p 53 expression and the presence of mutations when only exons 5-9 were examin ed. We then evaluated exon 4. Methods: DNA was sequenced from 217 gastric c ancers to detect exon 4 alterations. Codon 72 was examined by restriction e nzyme digestion. Results: Mutations were present in 3.2% of tumors. In addi tion, 2 polymorphic sites were found at codons 36 and 72, Polymorphisms at codon 36 were only found in 2 patients, In contrast, the codon 72 polymorph ism was very frequent. The genotype frequency was arg/arg (54%), arg/pro (3 3%), and pro/pro (14%). The genotype of the polymorphic site varied with ra ce (P = 0.001): 64% of whites had the arg/arg genotype, compared with 24% o f blacks, The difference in genotype by site, sex, or histological tumor ty pe was not statistically significant (P = 0.067), Conclusions: There are se veral exon 4 alterations in gastric cancers. These include the rare mutatio ns and the very rare codon 36 polymorphism. The most common change is the c odon 72 polymorphism, the genotype of which differs significantly with race . The more common arg/arg genotype in whites may explain why whites are mor e prone to develop cardiac cancer, whereas the more common proline allele i n blacks may explain why they are more prone to develop antral cancers. Fur ther studies are required to determine whether the codon 72 polymorphism af fects patient predisposition to gastric cancer.