Implications and Prognostic Value of K-ras Mutation for Early-Stage Lung Cancer in Women

作者：Heather H. Nelson, David C. Christiani, E.J. Mark, John K. Wiencke, John C. Wain, Karl T. Kelsey · 发表于：JNCI Journal of the National Cancer Institute · 年份：1999 · DOI：10.1093/jnci/91.23.2032 · 被引用次数：231 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

BACKGROUND: Because there is no clear consensus as to the predictive value of K-ras gene mutation for survival in patients with lung cancer, we examined the occurrence of K-ras mutations in a large, prospective case series of non-small-cell lung cancer (NSCLC). Our goals were to define the patient characteristics associated with K-ras mutation and to determine whether mutation of this gene might be a biomarker of patient prognosis. METHODS: Consecutive, newly diagnosed patients with lung cancer treated with potentially curative resection over a 4-year period were recruited for study. The mutation status of K-ras codon 12 in each patient's tumor DNA was determined by means of polymerase chain reaction-restriction fragment length polymorphism analysis of archived pathology specimens. Analyses were restricted to adenocarcinoma. RESULTS: There was a statistically significant association between female sex and K-ras mutation after adjustment for carcinogen exposures (odds ratio = 3.3; 95% confidence interval [CI] = 1.3-7.9); mutations were found only in smokers. Comparison of Kaplan-Meier curves indicated a strong association between K-ras mutation and decreased patient survival (two-sided P =.009); analysis stratified by pathologic staging groups revealed that this association was statistically significant only for stage I tumors (two-sided P =.002). Cox proportional hazards modeling indicated that K-ras codon 12 mutation was a statistically significant predictor of patient survi...