Risk Factors for Lung Cancer

Lung Cancer Risk Factors

Lung cancer is the most commonly diagnosed cancer in the world, accounting for 12.7% of all new cancers cases annually (McErlean and Ginsberg, 2011, p. 173). Lung cancer is also the most lethal, killing more people each year (18.2%) that any other type of cancer (Molina, Yang, Cassivi, Schild, and Adjei, 2008, p. 584; Brennan, Hainaut, and Boffetta, 2011, p. 399). There are very large geographical differences (30 to 60-fold) in the prevalence of lung cancer, with developing countries representing a full 55% of all new cases each year (McErlean and Ginsberg, 2011, p. 173). The geographical difference in incidence highlights the dominance of environmental risk factors in lung cancer etiology.

Types of Lung Cancer

Non-small cell lung cancer (NSCLC) is the most common type, representing 85% of all lung cancers (Molina, Yang, Cassivi, Schild, and Adjei, 2008, p. 584). The three types of NSCLC are squamous-cell carcinoma, adenocarcinoma, and large-cell carcinoma, with the first two types representing 80% of all lung cancer cases (Brennan, Hainaut, and Boffetta, 2011). The second most common type of lung cancer is small-cell lung carcinoma (SCLC). The main difference between NSCLC and SCLC are the cell types of origin, with the former arising from bronchial epithelial-cell precursors and the latter from neuroendocrine precursor cells.

Risk factors

Smoking cigarettes is by far the greatest risk factor for lung cancer globally, representing 75-90% of all lung cancer risk (McErlean and Ginsberg, 2011, p. 174-175). This is due to the presence of several carcinogens in tobacco smoke. Since these compounds are also present in second-hand smoke the risk of lung cancer for non-smoking bystanders is significantly elevated compared to unexposed non-smokers. Squamous-cell carcinoma and SCLC have been found to be associated more frequently with tobacco smoke exposure, although this difference is non-significant. The incidence of squamous-cell carcinoma and adenocarcinoma is declining and increasing, respectively, and is believed to be related to how the composition of cigarettes have changed over time.

Exposure to indoor radon gas is the second leading cause of lung cancer (McErlean and Ginsberg, 2011, p. 175). The ground in some geographic areas can produce significant amounts of radon gas that is otherwise diluted in the atmosphere, but if a building is constructed on top of these sources the gas can become trapped inside and expose inhabitants to high concentrations. Mine workers may also be exposed to significant concentrations of radon and other radioactive compounds. Inhalation of radon exposes lung tissue to significant amounts of ionizing radiation that destroys important cellular structures guarding against malignancy. For this reason, the combination of radon exposure and smoking synergistically increase the risk of lung cancer. Current estimates suggest that lung cancer risk increases 8 to 11% for every 100 Bq•m-3 increase in indoor ionizing radiation levels (Samet, 2011, p. 4), accounting for 12 to 14% of all lung cancer cases diagnosed each year (Bissett and McLaughlin, 2010, p. 47).

The balance of lung cancer cases that can't be attributed to being a smoker or radon exposure is due primarily to environmental carcinogen exposure (McErlean and Ginsberg, 2011, p. 175). This includes second-hand cigarette smoke, which increases the relative risk of lung cancer from 1.14 to 5.20 depending on the duration, composition, and concentration of the exposure (Molina, Yang, Cassivi, Schild, and Adjei, 2008, p. 585). Approximately 1.6% of all lung cancer cases can be attributed to second-hand cigarette smoke. Occupational exposure to carcinogens is estimated to be responsible for 5% of lung cancer cases (McErlean and Ginsberg, 2011, p. 175). These carcinogens include asbestos, silica, chromium, cadmium, nickel, arsenic, and beryllium, with asbestos contributing the biggest share.

A family history of lung cancer can also increase disease risk from 30 to 300%, depending on an individual's genetic makeup (Molina, Yang, Cassivi, Schild, and Adjei, 2008, p. 586). The mechanisms underlying the genetic predispositions have yet to be defined, but one scientist suggested that a disease-linked mutation in the nicotinic acetylcholine receptor could be increasing the risk of lung cancer by making nicotine more addictive.