Distribution of p53 and K-ras mutations in human lung cancer tissues.

Studies were performed to examine the mutational pattern of K-ras exons 1 and 2 and p53 exons 5-8 in lung cancer tissues from 27 Chinese patients (10 smokers, 17 non-smokers) using single-stranded conformational polymorphism and DNA sequencing. K-ras mutations were found in 13/27 tumors (48%); all mutations were clustered in exon 1 and distributed between codons 9 and 32. The frequency and number of patients with K-ras mutations between smokers and non-smokers were not different, except that a high frequency of G --> A transitions (11/11) was found in non-smokers. Among cell types, K-ras mutations were found in 7/13 (54%) squamous cell carcinoma (SC) and 5/12 (42%) adenocarcinoma (AC) patients. A --> T transversions (all six transversions) were present only in SC. In p53, 18/27 (67%) tumors contained mutations in exons 7 and 8, frequently at codons 226, 270, 275 and 281. The number of tumors with p53 mutations in smokers (70%) and in non-smokers (65%) was similar, and the mutation frequency did not differ except for a higher number of G --> A (6/7) and T --> C (5/6) transitions in non-smokers. Among cell types, the number of tumors with p53 mutations was 9/13 (69%) in SC and 8/12 (67%) in AC. The A --> G (11/16) transitions and A --> C (4/4) transversions in p53 were more frequent in SC than in AC (P < 0.04 for A --> G; P < 0.02 for A --> C). The varying mutation patterns in both the K-ras and p53 genes between smokers and non-smokers and among cell types suggest that other than cigarette smoke, environmental and dietary factors may also be involved in the genesis of lung cancer among these patients.