Although there are a variety of causes and risk factors for lung cancer, none are more clearly defined than smoking, which is implicated in approximately 85% of all lung cancers (Larsen 2011). Overall, smokers are about 25 times more likely than nonsmokers to develop lung cancer (Larsen 2011; ACS 2013a; ACS 2014c). Over half of newly-diagnosed lung cancers in the United States, however, occur in people who have already quit smoking, a testament to the long-term damage caused by tobacco smoke (Larsen 2011). Those exposed to secondhand smoke are at increased risk of developing lung cancer as well; one study estimated that workers exposed to atypically high levels of secondhand smoke may have up to a 13-fold increased risk of dying from lung cancer (NCI 2014e; Mayo Clinic 2014; O'Hanlon 2013; Siegel 2003).
Tobacco smoke has been reported to contain over 6000 chemicals, more than 70 of which have been shown to be carcinogenic. These include arsenic, benzene, benzo(a)pyrene, cadmium, and formaldehyde (Sanders 2008; Health Canada 2011). When inhaled, these compounds contribute to DNA damage, resulting in the mutation of genes involved in controlling cellular growth (Landi 2006).
Fortunately, long-term smoking cessation mitigates lung cancer risk; after 10 years without smoking, the likelihood of developing lung cancer is decreased 30–50% (NCI 2013d). However, it is unclear if former smokers have a better prognosis than patients still smoking at diagnosis. It is clear, however, that smoking cessation after diagnosis improves outcomes (Parsons 2010).
Family History and Genetic Predisposition
Several large studies have identified inherited genetic variations that increase the risk of lung cancer, some of which also increase the risk of nicotine dependence (Larsen 2011). Studies have found at least 3 key chromosomal regions that in populations of European descent are associated with the risk of lung cancer: sequence variants within the nicotinic acetylcholine receptor genes on chromosome 15, which are associated with the number of cigarettes smoked per day, nicotine dependence, and smoking-related diseases; sequence variants in a region on chromosome 5, which includes the TERT and the CLPTM1L genes; and a region on chromosome 6. Neither of the two latter regions appeared to be associated with smoking behavior (Rafnar 2011). Having a first-degree relative with lung cancer is associated with a roughly 50% increased risk of acquiring the disease; the risk increases to about 80% when the affected relative is a sibling (Cote 2012).
Previous Lung Disease
Many lung diseases, including chronic bronchitis, emphysema, pneumonia, and tuberculosis are associated with lung cancer development (Brenner 2012; Koshiol 2009). Specifically, people with emphysema and chronic bronchitis have a 2.44-fold and 1.47-fold increased risk, respectively, of developing lung cancer. Never smokers with a history of emphysema, pneumonia, or tuberculosis demonstrate a higher risk of lung cancer than those without (Brenner 2012). These diseases are major sources of inflammation in lung tissue, which is thought to contribute to cellular changes resulting in malignancy (Brenner 2012; Koshiol 2009; Engels 2008).
Carcinogenic Environmental Factors and Toxins
Several environmental factors are associated with lung cancer development, including exposure to asbestos, diesel engine exhaust, air pollution, pesticides, and heavy metals such as cadmium and nickel (Vermeulen 2014; Raaschou-Nielsen 2013; Clapp 2008; Offermans 2014; Wild 2009).
Radon, a radioactive gas released from the decay of uranium, thorium, and radium, can damage epithelial lung cells, leading to cancer. In fact, exposure to radon is the second leading cause of lung cancer in the United States, after smoking (NCI 2011).