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carcinogens have been defined, including asbestos, benzopyrene, arsenic, chromium, and nickel. High doses of radiation increase lung cancer risk. Radon and its decay products are associated with lung cancer in miners exposed to high levels of radon gas and are of concern because of the potential exposure in domestic environments. Other factors known to influence lung cancer risk include air pollution, the presence of other lung diseases, such as COPD and interstitial lung disease, and exposure to environmental tobacco smoke. Diet has also been implicated. Case-control and prospective studies have generally found that diets rich in fruits and vegetables are associated with lower risk for lung cancer. Finally, genetic susceptibility also plays a role in lung cancer. Many studies have shown that a history of lung cancer in a first-degree relative is associated with increased risk, and that this association may be of more significance in younger individuals. Genetically determined host factors may be important at many points in the cumulative steps leading to lung cancer, including the risk of nicotine dependence, carcinogen metabolic detoxification, activation of carcinogens, and the processes of DNA damage and repair. How is it prevented, treated, and managed? Prevention, treatment, staying healthy, prognosis Most lung cancer risk factors are modifiable and, therefore, can be minimized or eliminated. Cigarette smoking, occupational exposures, radon exposure, and environmental tobacco smoke all can be reduced. Cigarette smoking cessation at any age will decrease lung cancer risk. Though it never reaches the level of a never-smoker, the risk of lung cancer in an individual who quits smoking decreases with longer duration of abstinence. Community and public health initiatives increasingly limit exposure to second-hand smoke. Government regulation has reduced occupational exposure to most carcinogens. Whitebook_breathing_Ch11.indd 113 6/25/10 12:51:18 PM Lung Cancer Treatment for lung cancer is typically guided by stage, although individual factors, such as overall health and coexisting medical conditions, are important. Complete surgical removal is the best treatment, but it is only possible in patients with early stage disease. Chemotherapy is beneficial at most stages of disease, although it and radiation therapy are curative in only a minority of patients. Palliative therapy can improve the quality and often the length of life. A multidisciplinary approach that incorporates medical, surgical, and social support services generally renders the best care. The 1964 Surgeon General’s report on smoking, which reviewed 7,000 scientific articles, profoundly changed public attitudes and policy toward smoking. In the course of a decade, the percentage of Americans who believed that smoking causes cancer went from 44 to 78 percent. Whitebook_breathing_Ch11.indd 114 6/25/10 12:51:48 PM Chapter 11 Lung Cancer 115 Are we making a difference? Research past, present, and future Epidemiologic research has vastly improved our understanding of lung cancer risk factors and found them to be modifiable with appropriate interventions. Lung cancer is much less common in persons without identifiable risk factors. Applying this information to develop and implement prevention strategies has led to decreased smoking, which is now associated with a declining lung cancer rate in men and a plateauing rate in women in the United States. These data have induced legislative efforts to regulate tobacco and eliminate exposure to cigarette smoke in public areas. Although these regulations have already decreased the incidence of heart disease, it will take years to assess their impact on lung cancer. Lung cancer research seeks to improve methods for early diagnosis; understand genetic and molecular factors that influence carcinogenesis, tumor behavior, and outcomes; develop new treatments based on sound scientific knowledge; and individualize treatment based on patient situations and a better understanding of tumor biology. The U.S. Environmental Protection Agency (EPA) recommends that all homeowners test their house for radon, which is second only to smoking in causing lung cancer. Steve Cole /Getty Images Whitebook_breathing_Ch11.indd 115 6/25/10 12:51:53 PM Lung Cancer Chapter 11 116 There is unfortunately no reliable screening tool for early lung cancer detection. Screening studies have failed to show a clear increase in survival in highrisk patients. The National Lung Screening Trial is an ongoing, large, prospective study comparing yearly screening chest radiographs versus yearly screening computed tomography scans in persons at risk for lung cancer because of smoking. This study should increase our understanding of whether either of these means of early detection will decrease lung cancer mortality. The ability to study the entire genome now makes it possible to understand genetic variation not only between those with and without the disease, but also among those with different severities of illness. These studies also may give insight into the mechanism of disease and lead to potential therapeutic targets. For example, several studies have reported an association between lung cancer and a single genetic variant on chromosome 15. This site includes genes that code nicotinic acetylcholine receptors that are strongly associated with smoking behavior. Although the genetic risk alone for lung cancer is relatively small Although smoking has decreased among all teenagers, girls are now slightly more likely to smoke than boys. Steve Liss /TIME & LIFE Images /Getty Images Whitebook_breathing_Ch11.indd 116 6/25/10 12:52:06 PM Chapter 11 Lung Cancer 117 (it increases incidence by two- to three-fold), it may be magnified by interaction with environmental influences. Finding changes in the molecular pathways that regulate cell proliferation, programmed cell death (apoptosis), new blood vessel development (angiogenesis), invasion, and metastasis are critical to developing new treatments. A breakthrough in this area came with the discovery of the epidermal growth factor receptor (EGFR) signaling pathway, which is involved in many processes of human lung cancers. Molecular characterization of EGFR has facilitated description of its mutations, as well as the ability to identify the number of copies of the EGFR gene and quantification of its protein expression in malignant tissue. This has enabled patients’ tissues to be tested and classified with regard to EGFR mutational status. Specific inhibitors of the EGFR pathway have been developed for treatment of lung cancer. Selected EGFR mutations, high EGFR gene copy number, and EGFR protein over-expression have been reported to be predictive of response to treatment with EGFR antagonists. Therapeutic agents targeted to the EGFR pathway have been developed by the following strategies: 1) block the binding of the factor to the outside of the cell, 2) inactivate the receptor with anti-EGFR antibodies, and 3) block the intracellular effects of the signaling pathway with small molecules before they trigger action in the cell. The genetic profile associated with response to medical therapy against EGFR includes Asian heritage, female sex, nonsmoking status, and adenocarcinoma cell type, although benefit also may be observed in individuals without these characteristics. The ability to target therapy based on molecular characteristics of an individual tumor represents an enormous advance in treatment and an important step toward the goal of personalized lung cancer care. What we need to cure or eliminate lung cancer Steps to reduce and eliminate lung cancer began with the understanding of the central role of tobacco in this disease. Public awareness campaigns that reduce smoking and strong legislative action to eliminate tobacco smoke in public places and further decrease in cigarette use are saving lives. Attention to other risk factors, such as radon, should also diminish lung cancer incidence. Whitebook_breathing_Ch11.indd 117 6/25/10 12:52:06 PM Lung Cancer Chapter 11 118 Early diagnosis is an important factor in survival and would be greatly facilitated by identifying a simple marker of lung cancer. Because the lung is a difficult organ to sample, a blood test, swabs for cells in the mouth, or exhaled breath are being explored as surrogate indicators. It is hoped that reliably identifying cells and
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