Alterations in exon 4 of the p53 gene in gastric carcinoma.
OBJECTIVE
Our long-term goal was to evaluate the role of p53 in the prognosis of gastric cancer. We previously showed a discrepancy between p53 expression and the presence of mutations when only exons 5-9 were examined. We then evaluated exon 4.


METHODS
DNA was sequenced from 217 gastric cancers to detect exon 4 alterations. Codon 72 was examined by restriction enzyme digestion.


RESULTS
Mutations were present in 3.2% of tumors. In addition, 2 polymorphic sites were found at codons 36 and 72. Polymorphisms at codon 36 were only found in 2 patients. In contrast, the codon 72 polymorphism was very frequent. The genotype frequency was arg/arg (54%), arg/pro (33%), and pro/pro (14%). The genotype of the polymorphic site varied with race (P = 0.001): 64% of whites had the arg/arg genotype, compared with 24% of blacks. The difference in genotype by site, sex, or histological tumor type was not statistically significant (P = 0.067).


CONCLUSIONS
There are several exon 4 alterations in gastric cancers. These include the rare mutations and the very rare codon 36 polymorphism. The most common change is the codon 72 polymorphism, the genotype of which differs significantly with race. The more common arg/arg genotype in whites may explain why whites are more prone to develop cardiac cancer, whereas the more common proline allele in blacks may explain why they are more prone to develop antral cancers. Further studies are required to determine whether the codon 72 polymorphism affects patient predisposition to gastric cancer.
Shepherd
T
T
Department of Pathology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Tolbert
D
D
Benedetti
J
J
Macdonald
J
J
Stemmermann
G
G
Wiest
J
J
DeVoe
G
G
Miller
M A
MA
Wang
J
J
Noffsinger
A
A
Fenoglio-Preiser
C
C
D002288:Adenocarcinoma, Mucinous / Q000208:ethnology / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D002276:Carcinoid Tumor / Q000208:ethnology / Q000235:genetics; D018276:Carcinoma, Medullary / Q000208:ethnology / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005091:Exons / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D017354:Point Mutation; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D044465:White People / Q000235:genetics
D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53