Role of p 53 codon 72 polymorphism in EBV-related gastric cancer

Twenty-three EBV-positive cases (5.3%) were detected in 431 gastric cancer cases by EBV encoded small RNA1 (EBER1) in situ hybridization. p53 codon72 polymorphisms were evaluated in 23 EBV-positive gastric cancers by DNA direct sequencing; arginine (arg) was found in 7 (30.4%), proline (pro) in 0 (0%), and arg/pro in 16 (69.6%) cases. In 160 EBV-negative cases, arg was found in 88 (55.0%), pro in 10 (6.3%), and arg/pro in 62 (38.7%) tumors. The frequency of the arg/pro type was significantly higher in EBV-positive than negative cases (p<0.05). DNA mutations were analyzed in exon 4-8 of the p53 gene in 23 EBV-positive and age/sex-matched EBV-negative cases. There were seven homozygous mutations in five EBV-positive cases and five homozygous mutations in five EBV-negative cases. A nonsense mutation was included in one EBV-positive case and one negative case. On the other hand, there were six heterozygous mutations in four EBV-positive cases and two heterozygous mutations in two EBV-negative cases. Double mutations were found more in EBV-positive cases than negative cases. Five of six patients with heterozygous mutations were of the arg/pro type. The other tumor was of the arg type with double heterozygous mutations. It has been reported that an arg-containing allele is preferentially mutated in heterozygotes and mutant p53 binds and inhibits the apoptotic function of the p53 family proteins. Therefore, arg mutant protein in the patients with the arg/pro type may inhibit the apoptotic function. Such condition may be preferable for virus to survive.