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

应用EBV编码小RNA1 （EBER1）原位杂交技术，在431例胃癌患者中检测出EBV阳性23例（5.3%）。采用DNA直接测序法对23例ebv阳性胃癌患者的p53密码子72多态性进行了评价；精氨酸（arg） 7例（30.4%），脯氨酸（pro） 0例（0%），arg/pro 16例（69.6%）。在160例ebv阴性病例中，88例（55.0%）发现arg， 10例（6.3%）发现pro， 62例（38.7%）发现arg/pro。ebv阳性组arg/pro型出现频率显著高于阴性组（p<0.05）。在23例ebv阳性和年龄/性别匹配的ebv阴性病例中，分析了p53基因外显子4-8的DNA突变。5例ebv阳性病例有7个纯合突变，5例ebv阴性病例有5个纯合突变。1例ebv阳性病例和1例ebv阴性病例包括无义突变。另一方面，4例ebv阳性病例有6个杂合突变，2例ebv阴性病例有2个杂合突变。双突变在ebv阳性病例中多于阴性病例。6例杂合突变患者中有5例为arg/pro型。另一个肿瘤为双杂合突变的arg型。据报道，含有arg的等位基因在杂合子中优先突变，突变的p53结合并抑制p53家族蛋白的凋亡功能。因此，arg/pro型患者的arg突变蛋白可能抑制细胞凋亡功能。这样的条件可能更有利于病毒的生存。

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.