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

应用EBV编码的小RNA1(EBER1)原位杂交技术，在431例胃癌组织中检出23例EBV阳性(5.3%)。用DNA直接测序法检测了23例EBV阳性胃癌组织中p53基因密码子72的多态性，其中7例(30.4%)为精氨酸(Arg)，0例(0%)为Pro，16例(69.6%)为Arg/Pro。在160例EBV阴性肿瘤中，Arg阳性88例(55.0%)，Pro阳性10例(6.3%)，Arg/Pro阳性62例(38.7%)。EBV阳性组Arg/PRO频率显著高于阴性组(p&lt；0.05)。对23例EBV阳性和年龄/性别匹配的EBV阴性病例进行了p53基因外显子4-8的DNA突变分析。在5例EBV阳性病例中有7个纯合子突变，在5个EBV阴性病例中有5个纯合子突变。在1例EBV阳性和1例阴性病例中存在无义突变。另一方面，在4例EBV阳性病例中发现6个杂合子突变，在2个EBV阴性病例中发现2个杂合子突变。EBV阳性患者的双突变多于EBV阴性患者。6例杂合子突变患者中有5例为Arg/PRO类型。另1例为Arg型肿瘤，具有双重杂合性突变。有报道称，杂合子中含有Arg的等位基因优先发生突变，突变型P53结合并抑制P53家族蛋白的凋亡功能。因此，Arg/PRO型患者体内的Arg突变蛋白可能具有抑制细胞凋亡的作用。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.