P53, p21, and p73 gene polymorphisms in gastric carcinoma

The aim of this study was to evaluate the association of genetic polymorphisms of p53, p21, and p73 genes with susceptibility to gastric carcinoma (GC), its clinicopathologic features, and prognosis.

In a case-control study including 419 controls and 389 patients with sporadic GC, single nucleotide polymorphisms (SNPs) of p53 Arg72Pro, p21 Ser31Arg, and p73 G4C14-to-A4T14 at exon 2 were genotyped. Tumor tissue was immunostained with p53 and examined for mutations in exons 5 to 8 of p53 using PCR -based single strand conformational polymorphism analysis and direct sequencing.

The SNPs of p53, p21, and p73 genes were not significantly associated with susceptibility to GC. p53 SNP (Pro/Pro) was significantly associated with increased risks for the following subgroups: invasive infiltration-type carcinoma (odds ratio [OR], 2.09; 95% CI, 1.01 to 4.34; p = 0.048), carcinoma with peritoneal dissemination (OR, 3.42; 95%CI, 1.05 to 11.08; p = 0.04), and carcinoma with distant metastasis (OR, 3.90; 95% CI, 1.14 to 13.38; p = 0.03), but not with p53 immunoreactivity or mutations when compared with wild type. With respect to prognosis, p53 SNP (Pro/Pro) was an independent marker of poor overall survival in GC with TNM IB to IV stages (hazard ratio, 2.31; 95% CI, 1.14 to 4.69; p = 0.02), especially in GC treated by chemotherapy (hazard ratio, 2.17; 95% CI, 1.06 to 4.41; p = 0.03).

This study provides evidence supporting the association of p53 SNP Arg72Pro with GC with invasive phenotype, peritoneal dissemination, distant metastasis, chemoresistance, and poor prognosis.