Malignant non-small cell epithelial tumors of the lung are classified by the World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC). There are three main subtypes of non-small cell lung cancer (NSCLC), including the following:
Squamous cell carcinoma (25% of lung cancers).
Adenocarcinoma (40% of lung cancers).
Large cell carcinoma (10% of lung cancers).
There are numerous additional subtypes of decreasing frequency.
Lung cancer is the most commonly occurring noncutaneous cancer in men and women combined in the United States and is the leading cause of cancer deaths. In 2013 alone, it is estimated that there will be 228,190 new cases diagnosed, and 72,220 women and 87,260 men will die from this disease. The lung cancer death rate rose rapidly over several decades in both sexes, with a persistent decline for men commencing in 1991. From 2005 to 2009, death rates decreased by 2.8% per year in men and by 1.0% per year in women.
The most important risk factor for lung cancer (as for many other cancers) is tobacco use.[2,3] Cigarette smoking has been definitively established by epidemiologic and preclinical animal experimental data as the primary cause of lung cancer. This causative link has been widely recognized since the 1960s, when national reports in Great Britain and the United States brought the cancer risk of smoking prominently to the public's attention. The percentages of lung cancers estimated to be caused by tobacco smoking in males and females are 90% and 78%, respectively.
Environmental or secondhand tobacco smoke is also implicated in causing lung cancer. Environmental tobacco smoke has the same components as inhaled mainstream smoke, although in lower absolute concentrations; between 1% and 10%, depending on the constituent. Carcinogenic compounds in tobacco smoke include the polynuclear aromatic hydrocarbons (PAHs), including the classical carcinogen benzo[a]pyrene and the nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In rodents, total doses of both PAH and NNK that are similar to doses received by humans in a lifetime of smoking induce pulmonary tumors. Elevated biomarkers of tobacco exposure, including urinary cotinine, tobacco-related carcinogen metabolites, and carcinogen-protein adducts, are seen in passive or secondhand smokers.[6,7,8,9,10]
Many other exposures have been established as causally associated with lung cancer, but even the combined effect of these additional factors is very small compared with cigarette smoking. These additional causal factors are primarily related to occupational exposures to agents such as asbestos, arsenic, chromium, nickel, and radon. Radon, a naturally occurring gas, is of relevance to the general public because of the potential exposure in homes.