近日肿瘤研究者发现，烟民和非烟民所得的肺癌，其实有着本质区别。该研究是约翰·霍普金斯大学（JOHNS HOPKINS）的最新研究发现，该结论表明，对肺癌的治疗也应该有所不同。
约翰·霍普金斯大学金梅尔肿瘤中心，分管临床研究工作的副主任查尔斯·鲁丁说：“不吸烟者得的肺癌在基因、细胞和分子生物学方面的性质与吸烟相关肺癌是不同的，这一点目前越来越清楚了。同时，现在也有非常好的证据表明，对于不吸烟的人，防治肺癌的策略可能也与吸烟者不同。”
这里的不吸烟者，是指那些一生吸烟少于100支的人。对于这些人群，由于他们没有吸烟史，医生很少会怀疑他们得了肺癌，而肺癌往往在晚期表现出咳嗽、胸痛，经常被误诊为呼吸道疾病，使用抗生素或着抗哮喘药物进行治疗。鲁丁补充道。
“从不吸烟的患者对一类叫表皮生长因子受体抑制剂（EGFR inhibitors）的药物反应更好，因为这类患者表皮生长因子受体基因（EGFR gene）突变的可能性更大一些。”鲁丁进一步解释道。
EGFR通常促进细胞的生长发育，一旦发生基因变异，会使细胞不受控制地生长。细胞不受控制地生长，这正是癌症的特征。
对于临床前景，他说：“针对不吸烟者的基因改变进行靶向治疗，这有些其它的成功例子，比如针对有EML4－ALK基因改变的肿瘤进行的治疗。专门对这一人群进行的全基因水平组相关性研究可以告诉我们更多信息。“
在美国人口癌症相关死因排名中，不吸烟者所患肺癌排在第六位。
接触二手烟和氡气被认为是造成不吸烟者罹患这种疾病的重要因素。但是，大约有一半不吸烟者肺癌病例无法用已知的危险因素进行解释。这些已知危险因素还包括：石棉、烧薪材的室内火炉和油烟。
南加利福尼亚大学预防医学系的乔纳森·萨梅特教授和弗洛拉·L·桑顿都表示：“除了二手烟和氡接触外，我们仍然很难解释不吸烟者得肺癌的原因。”
鲁丁也表示，不吸烟者的肺癌状况往往在妇女和东亚的一些人群中更为常见，可能是由于妇女更多地接触由烹饪油和燃柴火炉等生成的室内污染。
在美国，非吸烟者肺癌占肺癌病例数的10至15%，每年约20,000例。同时，所有类型肺癌患者的生存机率都不高。
这项研究成果分为三篇论文发表在在9月15日的《临床癌症研究》（Clinical Cancer Research）杂志上。这项研究由航空乘务员医学研究所（Flight Attendant Medical Research Institute）资助。（生物谷Bioon.com）
生物谷推荐原始出处：
Clinical Cancer Research September 15, 2009 15, 5622
Lung Cancer in Never Smokers: A Call to Action
Charles M. Rudin, Erika Avila-Tang and Jonathan M. Samet
Johns Hopkins University, Baltimore, Maryland
The causative association between tobacco use and lung cancer is a well-established fact. However, lung cancer also occurs, at surprisingly high rates, in lifelong never smokers. In fact, lung cancer in never smokers is among the leading causes of cancer-related mortality. This CCR Focus summarizes recent data, identifies knowledge deficits, and suggests future research directions with regard to this critically important subset of lung cancer patients.
Clinical Cancer Research September 15, 2009 15, 5626
Lung Cancer in Never Smokers: Clinical Epidemiology and Environmental Risk Factors
Jonathan M. Samet1, Erika Avila-Tang1, Paolo Boffetta2, Lindsay M. Hannan3, Susan Olivo-Marston4, Michael J. Thun3 and Charles M. Rudin1
1Johns Hopkins University, Baltimore, Maryland;
2International Agency for Research on Cancer, Lyon, France; 3American Cancer Society, Atlanta, Georgia; and 4National Cancer Institute, Bethesda, Maryland
More than 161,000 lung cancer deaths are projected to occur in the United States in 2008. Of these, an estimated 10 to 15% will be caused by factors other than active smoking, corresponding to 16,000 to 24,000 deaths annually. Thus lung cancer in never smokers would rank among the most common causes of cancer mortality in the United States if considered as a separate category. Slightly more than half of the lung cancers caused by factors other than active smoking occur in never smokers. As summarized in the accompanying article, lung cancers that occur in never smokers differ from those that occur in smokers in their molecular profile and response to targeted therapy. These recent laboratory and clinical observations highlight the importance of defining the genetic and environmental factors responsible for the development of lung cancer in never smokers. This article summarizes available data on the clinical epidemiology of lung cancer in never smokers, and several environmental risk factors that population-based research has implicated in the etiology of these cancers. Primary factors closely tied to lung cancer in never smokers include exposure to known and suspected carcinogens including radon, second-hand tobacco smoke, and other indoor air pollutants. Several other exposures have been implicated. However, a large fraction of lung cancers occurring in never smokers cannot be definitively associated with established environmental risk factors, highlighting the need for additional epidemiologic research in this area.
Clinical Cancer Research September 15, 2009 15, 5646
Lung Cancer in Never Smokers: Molecular Profiles and Therapeutic Implications
Charles M. Rudin1, Erika Avila-Tang1, Curtis C. Harris2, James G. Herman1, Fred R. Hirsch3, William Pao4, Ann G. Schwartz5, Kirsi H. Vahakangas6 and Jonathan M. Samet1
1Johns Hopkins University, Baltimore, Maryland;
2National Cancer Institute, Bethesda, Maryland;
3University of Colorado, Denver, Colorado;
4Memorial Sloan-Kettering Cancer Center, New York, New York;
5Wayne State University, Detroit, Michigan; and
6University of Kuopio, Kuopio, Finland
The majority of lung cancers are caused by long term exposure to the several classes of carcinogens present in tobacco smoke. Although a significant fraction of lung cancers in never smokers may also be attributable to tobacco, many such cancers arise in the absence of detectable tobacco exposure, and may follow a very different cellular and molecular pathway of malignant transformation. Recent studies summarized here suggest that lung cancers arising in never smokers have a distinct natural history, profile of oncogenic mutations, and response to targeted therapy. The majority of molecular analyses of lung cancer have focused on genetic profiling of pathways responsible for metabolism of primary tobacco carcinogens. Limited research has been conducted evaluating familial aggregation and genetic linkage of lung cancer, particularly among never smokers in whom such associations might be expected to be strongest. Data emerging over the past several years show that lung cancers in never smokers are much more likely to carry activating mutations of the epidermal growth factor receptor (EGFR), a key oncogenic factor and direct therapeutic target of several newer anticancer drugs. EGFR mutant lung cancers may represent a distinct class of lung cancers, enriched in the never-smoking population, and less clearly linked to direct tobacco carcinogenesis. These insights followed initial testing and demonstration of efficacy of EGFR-targeted drugs. Focused analysis of molecular carcinogenesis in lung cancers in never smokers is needed, and may provide additional biologic insight with therapeutic implications for lung cancers in both ever smokers and never smokers.
