p53 polymorphism and p21WAF1/CIP1 haplotype in the intestinal gastric cancer and the precancerous lesions

The development of intestinal gastric carcinoma involves several precancerous stages. The environmental factor plays an important role in gastric carcinogenesis, while the host's genetic makeup may influence the susceptibility to cancer. In this study we investigated correlations of the p53 variations at codon 72 and p21(WAF1/CIP1) haplotype with the risk of intestinal gastric carcinoma. Forty-eight intestinal gastric carcinoma cases (GC), 96 chronic atrophic gastritis (CAG), 96 intestinal metaplasia (IM) and 96 dysplasia (DYS) controls were enrolled in this study. The p53 codon 72 proline allele carriers were found to be more susceptible to progress to GC than to IM (OR = 2.22, 95%CI = 1.05-4.70, P = 0.038). Patients carrying homozygous p21(WAF1/CIP1) haplotype A, which contains the serine at codon 31, the cytidine at the 16th base of the second intron, and the cytidine at the 70th base of the exon 3 were more prone to develop GC than to reach the IM or DYS stage (IM versus GC, OR = 3.35, 95%CI = 1.11-10.15; DYS versus GC, OR = 3.27, 95%CI = 1.09-9.80, P = 0.035). The combination of p53 codon 72 variation with the p21(WAF1/CIP1) haplotype further distinguished the risk of GC from IM precancerous lesion (OR = 9.31, 95% CI = 1.77-48.85, P = 0.08). These results suggest that p53 and/or p21(WAF1/CIP1) genotype may influence the progression during gastric tumorigenesis.