The development of lung cancer is the culmination of multistep carcinogenesis. Genetic damage caused by chronic exposure to carcinogens, such as those in cigarette smoke, is the driving force behind the multistep process. Evidence of genetic damage is the association of cigarette smoking with the formation of the DNA adducts in human lung tissue. A strong link between tobacco smoke and lung carcinogenesis has been established by molecular data.[17,18]
Secondhand tobacco smoke
Secondhand tobacco smoke is also an established cause of lung cancer. Secondhand smoke has the same components as inhaled mainstream smoke, though in lower absolute concentrations, between 1% and 10% depending on the constituent. Carcinogenic compounds in tobacco smoke include the polycyclic 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). Elevated biomarkers of tobacco exposure, including urinary cotinine, urinary NNK metabolites, and carcinogen-protein adducts, are seen in those who are exposed to secondhand cigarette smoke.[20,21,22]
A positive family history of lung cancer is a risk factor for lung cancer. The results of a meta-analysis of epidemiologic studies indicated that those with a positive family history of lung cancer were at approximately twice the risk of lung cancer compared with those with no affected relatives. Cigarette smoking behavior tends to run in families and family members are exposed to secondhand smoke, so the extent to which measured family history represents a genetic predisposition to lung cancer independent of the shared risk factor of cigarette smoking is uncertain.
Human immunodeficiency virus (HIV) infection
HIV infection has been observed to be statistically associated with an increased lung cancer risk; for example, the results of a meta-analysis of 13 studies indicated HIV-infected individuals had a 2.6-fold higher risk of lung cancer than non-HIV-infected individuals (standard incidence ratio = 2.6; 95% confidence interval [CI] 2.1–3.1). The clinical significance of this association remains to be elucidated, as it raises the possibility that HIV infection increases susceptibility to lung cancer, but may merely reflect the high smoking prevalence (study estimates ranged from 59% to 96%) among those infected with HIV compared with the general population (smoking prevalence approximately 20%).
Other environmental causes of lung cancer
Occupational exposures to lung carcinogens
Several environmental exposures other than tobacco smoke are causally associated with lung cancer, but the proportion of the lung cancer burden due to these exposures is small compared with cigarette smoking. Many lung carcinogens have been identified in studies of high occupational exposures. Considered in total, occupational exposures have been estimated to account for approximately 10% of lung cancers. These carcinogens include asbestos, radon, tar and soot (source of PAHs), arsenic, chromium, and nickel. For many of these workplace carcinogens, cigarette smoking interacts synergistically to increase the risk. In developed countries, workplace exposures to these agents have largely been controlled.