Riely Gregory J, Kris Mark G, Rosenbaum Daniel, Marks Jenifer, Li Allan, Chitale Dhananjay A, Nafa Khedoudja, Riedel Elyn R, Hsu Meier, Pao William, Miller Vincent A, Ladanyi Marc
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Clin Cancer Res. 2008 Sep 15;14(18):5731-4. doi: 10.1158/1078-0432.CCR-08-0646.
KRAS mutations are found in approximately 25% of lung adenocarcinomas in Western countries and, as a group, have been strongly associated with cigarette smoking. These mutations are predictive of poor prognosis in resected disease as well as resistance to treatment with erlotinib or gefitinib.
We determined the frequency and type of KRAS codon 12 and 13 mutations and characterized their association with cigarette smoking history in patients with lung adenocarcinomas.
KRAS mutational analysis was done on 482 lung adenocarcinomas, 81 (17%) of which were obtained from patients who had never smoked cigarettes. KRAS mutations were found in 15% (12 of 81; 95% confidence intervals, 8-24%) of tumors from never smokers. Similarly, 22% (69 of 316; 95% confidence intervals, 17-27%) of tumors from former smokers, and 25% (21 of 85; 95% confidence intervals, 16-35%) of tumors from current smokers had KRAS mutations. The frequency of KRAS mutation was not associated with age, gender, or smoking history. The number of pack years of cigarette smoking did not predict an increased likelihood of KRAS mutations. Never smokers were significantly more likely than former or current smokers to have a transition mutation (G-->A) rather than the transversion mutations known to be smoking-related (G-->T or G-->C; P < 0.0001).
Based on our data, KRAS mutations are not rare among never smokers with lung adenocarcinoma and such patients have a distinct KRAS mutation profile. The etiologic and biological heterogeneity of KRAS mutant lung adenocarcinomas is worthy of further study.
在西方国家，约25%的肺腺癌中存在KRAS突变，总体而言，这些突变与吸烟密切相关。这些突变预示着手术切除疾病的预后不良以及对厄洛替尼或吉非替尼治疗的耐药性。
我们确定了肺腺癌患者中KRAS密码子12和13突变的频率和类型，并描述了它们与吸烟史的关联。
对482例肺腺癌进行了KRAS突变分析，其中81例（17%）来自从不吸烟的患者。从不吸烟者的肿瘤中有15%（81例中的12例；95%置信区间，8 - 24%）发现KRAS突变。同样，既往吸烟者的肿瘤中有22%（316例中的69例；95%置信区间，17 - 27%），当前吸烟者的肿瘤中有25%（85例中的21例；95%置信区间，16 - 35%）存在KRAS突变。KRAS突变频率与年龄、性别或吸烟史无关。吸烟包年数并不能预测KRAS突变可能性的增加。从不吸烟者比既往或当前吸烟者更有可能发生转换突变（G→A），而不是已知与吸烟相关的颠换突变（G→T或G→C；P < 0.0001）。
基于我们的数据，KRAS突变在从不吸烟的肺腺癌患者中并不罕见，且这类患者具有独特的KRAS突变谱。KRAS突变型肺腺癌的病因学和生物学异质性值得进一步研究。
