Hong Kong lung cancer shows an unique high incidence and mortality in both sexes, especially in females. This study comprises 188 cases including 98 NSCLC, 33 SCLC, 39 bronchiectasis patients, and 27 healthy individuals. Molecular markers including p53, MDM2, L-myc, c-erbB-2, and GSTM1 were studied by techniques including the PCR, PCR-SSCP, DNA sequencing, immunostaining, RT-PCR, cDNA sequencing, and p53 functional assays. Results showed that there was a significant departure of the L-myc genotypes from Hardy-Weinberg equilibrium in female lung cancer patients. The L allele was associated with a poorer survival rate. In addition, an ethnic difference of the L-myc genotypes behveen Chinese and African Americans was observed. Patients with the GSTMl-null gene have a significantly longer s...[ Read more ]

Hong Kong lung cancer shows an unique high incidence and mortality in both sexes, especially in females. This study comprises 188 cases including 98 NSCLC, 33 SCLC, 39 bronchiectasis patients, and 27 healthy individuals. Molecular markers including p53, MDM2, L-myc, c-erbB-2, and GSTM1 were studied by techniques including the PCR, PCR-SSCP, DNA sequencing, immunostaining, RT-PCR, cDNA sequencing, and p53 functional assays. Results showed that there was a significant departure of the L-myc genotypes from Hardy-Weinberg equilibrium in female lung cancer patients. The L allele was associated with a poorer survival rate. In addition, an ethnic difference of the L-myc genotypes behveen Chinese and African Americans was observed. Patients with the GSTMl-null gene have a significantly longer survival time. The expression of MDM2 and c-erbB-2 was 34% and 44%, respectively, in NSCLC tissues. MDM2 expression was associated with more aggressive stages of NSCLC. A polymorphism was detected in intron 2 of the p53 gene giving rise to three genotypes: A1/A1, A1/A2, and A2/A2. In blood, a significant decrease in the A1/A1 and an increase in the A1/A2 and A2/A2 genotypes from SCLC patients were demonstrated. In tumor tissue, the A1/A1 genotype occurred more frequently than in the blood from adenocarcinoma patients. Furthermore, a hot spot of point mutations was detected at this p53 intron 2 polymorphic site, with a total rate of mutations of 15.1%. For the p53 functional assay, seven out of eight tumor samples, which showed overexpression of p53 protein detected by immunostaining techniques but no detectable aberrations found by sequencing and RFLP analyses, showed abnormal p53 gene expression. These results provide the evidence that p53 mutations occurring outside common hot spots may play a crucial role in Hong Kong lung cancer. These mutations probably arise as the result of somatic events. It is clear that the carcinogenesis of the lung results from multiple genetic changes which all contribute to the development of this disease.