吸烟指数与肺癌患者支气管肺泡灌洗液中的K-ras基因突变(英文)

Cigarette smoking index and K-ras gene mutation in bronchoalveolar lavage fluid in patients with lung cancer

背景:肺癌的高发与许多因素有关,吸烟是重要原因之一,及早诊断对肺癌治疗尤其重要。目的:探讨肺癌患者吸烟与支气管肺泡灌洗液中细胞K-ras基因突变的关系。设计:以患者为研究对象的随机对照实验研究。单位:一所大学放射医学与公共卫生学院卫生毒理学教研室,一所大学医院呼吸内科。对象:选择在苏州大学第二附属医院1999-07/2001-09住院及门诊接受经纤维支气管镜行支气管肺泡灌洗术并取得细胞学或病理学确诊的肺癌、良性疾病患者。方法:应用聚合酶链反应结合限制性片段长度多态性分析法,检测37例吸烟肺癌患者、25例非吸烟肺癌患者以及20例肺良性疾病患者支气管肺泡灌洗液中细胞K-ras基因第12位密码子突变的情况。主要观察指标:K-ras基因第12位密码子突变。结果:肺癌患者K-ras基因突变率为36%(22/62),肺良性疾病患者中未发现K-ras基因突变。重度吸烟者的突变率(69%)显著高于中度(31%)和轻度吸烟者(25%),以及非吸烟者(20%)。突变的发生与患者的年龄及吸烟史相关,而与性别、TNM分型无关。结论:吸烟可能是导致K-ras基因突变的诱因之一;支气管肺泡灌洗液中K-ras基因突变的检测对预测吸烟者肺癌的发生和早期诊断,具有重要的临床价值。

BACKGROUND:Cigarette smoking has been recognized as one of the high risk facto rs in carcinogenesis of lung cancer.Early diagnosis of lung cancer may be of cli nical therapy value. OBJECTIVE:To explore the mutation of K ras oncogene in bronchoalveolar lavage fluid(BALF) in order to reveal its relationship with cigarette smoking in lung cancer patients. DESIGN:Randomized controlled trial based on the patients. SETTING:Department of Toxicology,College of Radiology and Public Health of a u niversity,and Department of Respiratory Medicine of a university hospital. PARTICIPANTS:The out patients and inpatients in the Second Affiliated Hospita l of Soochow University between June 1999 and September 2001 were included.The p atients were confirmed to have lung cancer or innocuous diseases by fiber bronch oscopy through bronchoalveolar lavage(BAL) and cytological or pathological exami nation. METHODS:BALF samples were obtained from 37 smoking patients with lung cancer a nd 25 nonsmoking patients with lung cancer,and 20 with benign pulmonary diseases in the Second Affiliated Hospital of Soochow University.They were detected for K ras codon 12 mutations using polymerase chain reaction with restriction fragm ent length polymorphism(PCR RFLP). MAIN OUTCOME MEASURES:Codon 12 mutations of K ras gene. RESULTS:K ras mutation in patients with lung cancer was found to have an ave rage frequency of 36%(22/62)but no K ras gene mutation was detected in patient s with benign pulmonary diseases. The mutation frequency in heavy smokers(69%) was higher than that in moderate smokers(31%),mild smokers(25%) and nonsmokers (20%).The mutation was related to age and history of smoking, but not to sex an d TNM classification. CONCLUSION:Cigarette smoking may be correlated with the mutation of K ras ge ne.Early detection of K ras mutation in BALF may be of clinical value,which hel ps the identification and diagnosis of smoking related lung cancer.