Detection and evaluation of p53 intron 2 polymorphism in lung carcinomas in Hong Kong.
A polymorphism in intron 2 of the p53 gene, which gives rise to 2 alleles, A1 and A2, was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct DNA-sequencing techniques. The distribution of this allele in the peripheral blood in the Chinese population comprising 27 healthy individuals, 30 bronchiectasis patients, 34 non-small-cell lung cancer (NSCLC) patients and 27 SCLC patients was analyzed. The genotypic distributions for this marker were significantly different between the blood of healthy individuals and SCLC patients. There was no significant difference between genotypes of Caucasians and Chinese. Tumors, normal lungs and peripheral blood of 83 adenocarcinoma and 10 squamous cell carcinoma patients were also studied. There was a significant difference in the distribution of the genotypes detected in tumor tissues vs. blood of adenocarcinoma patients. The frequency of detection of the A1/A1 genotype in the tumor tissues was increased in adenocarcinoma patients as compared with the blood of adenocarcinoma patients and was decreased in the blood of SCLC patients as compared with the blood of healthy individuals. Survival rates in Hong Kong adenocarcinoma patients with the A1/A1 genotype were lower than those in patients with A1/A2 and A2/A2 genotypes up to 30 months post-operation. Point mutations were detected at the p53 intron 2 polymorphic locus in NSCLC specimens, with a mutation rate of 15.4% (8/52). All mutations were GC transversions. The significance of this instability in p53 intron 2 remains to be elucidated.
Ge
H
H
Department of Biology, Hong Kong University of Science and Technology, Hong Kong.
Lam
W K
WK
Lee
J
J
Wong
M P
MP
Fu
K H
KH
Yew
W W
WW
Lung
M L
ML
D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D044466:Asian People; D001483:Base Sequence; D001987:Bronchiectasis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D005260:Female; D016158:Genes, p53; D006723:Hong Kong; D006801:Humans; D007438:Introns; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012907:Smoking; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044465:White People
D016159:Tumor Suppressor Protein p53