Carcinogenesis Advance Access originally published online on July 7, 2004
Carcinogenesis 2004 25(11):2201-2206; doi:10.1093/carcin/bgh229
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Carcinogenesis vol.25 no.11 © Oxford University Press 2004; all rights reserved.
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p53 polymorphism and p21WAF1/CIP1 haplotype in the intestinal gastric cancer and the precancerous lesions
1 Beijing Institute for Cancer Research, School of Oncology, Peking University, Beijing, China, 2 Chinese National Human Genome Center, Beijing, China, 3 Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, 4 Inner Mongolia Medical College, Huhhot, China and 5 Department of Cell Biology and Human Genetics, Peking University, Beijing, China
6 To whom correspondence should be addressed Email: keyang{at}mx.cei.gov.cn
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 p21WAF1/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 p21WAF1/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 p21WAF1/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 p21WAF1/CIP1 genotype may influence the progression during gastric tumorigenesis.
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