Smokers are not the only people at increased risk from exposure to tobacco smoke. "Passive smoking" from environmental tobacco smoke also increases the risk of lung cancer death. According to the Environmental Protection Agency (EPA), each year about 3000 nonsmoking adults die of lung cancer as a result of breathing the smoke of others' cigarettes. Analysis has shown that thesidestream smoke emitted from a smoldering cigarette between puffs contains virtually all carcinogenic compounds that have been identified in the mainstream smoke inhaled by smokers. Even though passive smokers are exposed to much lower concentrations of these carcinogens than active smokers, environmental tobacco smoke has become the only agent ever classified by the EPA as a human carcinogen forwhich an increased cancer risk has actually been observed at typical environmental levels of exposure.14 The risk of dying of lung cancer is 30% higher for a nonsmoker living with a smoker than for those living in a totally tobacco-free household.15
Cigarette Smoke Composition
Dozens of compounds have been identified in cigarette smoke, both particles (solid phase) and gases (vapor phase). Morethan 60 of these agents have been shown to be carcinogenic in laboratory animals, and some of them are also carcinogenic in humans, including benzo[a] pyrene, a polycyclic aromatic hydrocarbon; aromatic amines; formaldehyde; benzene; and miscellaneous inorganic and organic compounds. Tobacco also contains specific carcinogens related to nicotine, such as4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a strong carcinogen in rodents.16 Following 5 to 20 years of exposure to these agents, certain changes occur in airway epithelium as described in the next sections, leading in some cases to the development of cancer.10
Lung Cancer in Women
For most of the past 100 years, lung cancer has generally been thought of as a disease affecting primarily men. In the past several decades,however, the incidence of lung cancer has risen among women in the United States and most other parts of the world. Although incidence is still higher among men than women, the gap has narrowed and lung cancer has become the leading cause of cancer death among American women. The rise in rates of lung cancer among women has paralleled the increase in the prevalence of cigarette smoking. Just as inmen, the majority (85-90%) of lung cancers among women are considered the result of smoking. There is accumulating evidence suggesting that the development of lung cancer is different in women than in men. For example, women smokers are more likely than men to develop adenocarcinoma of the lung, and women who have never smoked are more likely to develop lung cancer than men who have never smoked.Furthermore, the 5-year survival rate for women who have lung cancer is 15.6%, while it is 12.4% for men; women survive longer after surgical resection of early-stage lung cancer as well as after treatment of metastatic disease; female sex has been associated with longer survival in SCLC as well. Hormonal, genetic, and metabolic differences between the sexes are believed to account for theseclinical differences. Indeed, estrogens were found to be involved in lung carcinogenesis, either by acting as estrogen receptor ligands and activating cellular proliferation pathways, or by metabolic activation to reactive intermediates that can produce DNA adducts and cause oxidative damage.17,18
Since smoking remains the primary cause of lung cancer, the differences in the clinical profile of thedisease between the sexes have been attributed to different response to tobacco carcinogens. Indeed, in the 1990s, several case-control studies indicated that relative risks of lung cancer associated with specific amounts and duration of cigarette smoking may actually be higher among women than among men. Bain and colleagues recently performed a meta-analysis on prospective cohorts to examine this...