Molecular analysis of etiological factors and malignant degrees for non-small cell lung cancer

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74 resected squamous cell carcinomas (sqs) and 239 adenocarcinomas were analyzed for p53 mutation : Any relationships between tumor location of sqs or subtype of adenocarcinomas, smoking, and p53 mutation patterns were then examined focusing on varying etiological factors. Our hypothesis was, that G→T transversion of p53 gene is caused by direct action of carcinogens contained in tobacco smoke on DNA, and that G→A transition at CpG (CpG→A) sites of the gene is caused by endogenous mechanisms. The same adenocarcinoma cases were also analyzed to determine what type of combined mutation status on p53 and k-ras affects malignancy of the tumors more strongly.Results:1) Sqs were divided into three types by location - central, intermediate and periphera l; the highest frequencies of CpG→A in the central type, G→T in the intermediate and other mutations in the peripheral, were observed. 2)Adenocarcinomas were divided into five types - hobnail, columnar, goblet, polygonal and mixed. Of these, the hobnail type showed a low p53 mutation frequency with the highest CpG→A rate, the columnar and polygonal types had a high mutation frequency with the highest G→T rates, and the mixed type showed intermediate frequency of p53 with the highest other base change. 3)Five year survival was the highest for adenocarcinomas with the combination of non-mutated p53 and k-ras, followed by the combination of mutated p53 and non-mutated k-ras, and then the combination of non-mutated p53 and mutated k-ras, with the combination of mutated p53 and k-ras having the lowest survival.The results show that etiological factors vary depending on locations of sqs and subtype of adenocarcinomas ; the worst malignancy was adenocarcinomas with the combined status on mutated p53 and k-ras.