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 alle les, A1 and A2, was analyzed by polymerase chain reaction-single stran d conformation polymorphism (PCR-SSCP) and direct DNA-sequencing techn iques. The distribution of this allele in the peripheral blood in the Chinese population comprising 27 healthy individuals, 30 bronchiectasi s patients, 34 non-small-cell lung cancer (NSCLC) patients and 27 SCLC patients was analyzed. The genotypic distributions for this marker we re significantly different between the blood of healthy individuals an d 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 th e genotypes detected in tumor tissues vs. blood of adenocarcinoma pati ents. The frequency of detection of the A1/A1 genotype in the tumor ti ssues was increased in adenocarcinoma patients as compared with the bl ood of adenocarcinoma patients and was decreased in the blood of SCLC patients as compared with the blood of healthy individuals. Survival r ates 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. (C) 1996 Wiley- Liss, Inc.