Analysis of K-ras gene mutations in lung carcinomas: Correlation with gender, histological subtypes, and clinical outcome

Purpose: Lung cancer is respectively the leading and second-leading cause of cancer deaths among women and men in Taiwan. The commonest pathological type of lung carcinoma found in Taiwan is adenocarcinoma, and it has been documented that K-ras oncogene mutation occurs in a subset of lung adenocarcinoma. We therefore investigated the mutation spectrum and clinicopathological significance of K-ras oncogene mutations in lung cancer patients in Taiwan. Methods: The lung tumors were surgically resected from 84 lung cancer patients. DNA was isolated and the mutation spectrum was examined by direct sequencing. These data were also correlated with the clinicopathological characteristics of patients. Results: K-ras gene mutations were detected in 5 cases among the 84 patients investigated (6.0%). The majority of mutations occurred in exon 1 (80%, 4 of 5) and were located mainly in codons 12 and 13. Two patients had G · C → T · A transversions and 2 patients had G · C → A · T transitions. Notably, 1 patient had a G · C base-pair deletion from the contiguous G C base pairs located between codons 68 and 69. All mutations occurred in male patients who were smokers. The incidences of K-ras gene mutation among male and female patients with adenocarcinoma were 13% and 0% respectively. Patients with K-ras gene mutation survived for shorter periods than those without mutations (P = 0.08, by the log-rank test). Conclusions: The incidence of K-ras gene mutations for male and female patients with adenocarcinoma was 13% and 0% respectively. Thus, the role of K-ras in the development of lung adenocarcinoma among Chinese men who are predominantly smokers is not significantly different from that in other populations worldwide. However, K-ras mutations may not be associated with adenocarcinoma among women in Taiwan, who are virtually all nonsmokers.