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Age-associated Increase of Codon 72 Arginine p53 Frequency in Gastric Cardia and Non-Cardia Adenocarcinoma

Division of Surgery [Z-W. Z., P. N., A. H., D. A., J. H.] and Department of Histopathology [M. M.], Bristol Royal Infirmary, University of Bristol, Bristol BS2 8HW; Department of Histopathology [R. F.] and Cancer Research UK; Skin Tumour Laboratory, Centre for Cutaneous Research [A. S.], St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London E1 2AD; and Faculty of Medicine, University of Glasgow, Glasgow, [M. J. G. F.], United Kingdom

Purpose: A common polymorphism of the tumor suppressor gene TP53 at codon 72 has been associated with human cancer susceptibility and prognosis. To examine the role of the polymorphism in the gastric adenocarcinoma, we examined 397 patients with or without the cancer.

Experimental Design: DNA samples were extracted from archived gastric tumor tissues and/or normal tissues of gastric adenocarcinoma and noncancer patients. The TP53 codon 72 genotypes were determined by PCR-RFLP.

Results: The overall genotype frequencies for Pro/Pro, Arg/Pro, and Arg/Arg were 7.3, 45.1, and 47.6%, respectively. A significant stepwise increased frequency of codon 72 Arg p53 with age was observed in patients with gastric cancer, but not in noncancer patients (P = 0.01). Patients with gastric cardia cancer had a significantly higher frequency of homozygous Arg allele than those with non-cardia tumors (P = 0.03) or than noncancer patients. After adjustment for age and gender, a logistic regression analysis suggested that the risk for a p53 Arg homozygous patient to develop cardia cancer is 3.1 95% confidence interval, 1.4–7.3) times greater than for p53 Pro homozygous and p53 Arg/Pro heterozygous patients. No close relationship was observed among patient gender, tumor histological type, p53 protein expression, and codon 72 genotype distribution.

Conclusions: These findings indicate that codon 72 Arg p53 may be associated with a prolonged survival for patients who have had gastric adenocarcinoma, especially non-cardia adenocarcinoma. It may confer, however, a different role on patients who suffer cardia gastric adenocarcinoma.

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