Globally, lung cancer is the leading cancer in terms of incidence and mortality and accounts for the greatest loss in years of healthy life (International Agency for Research on Cancer and Cancer Research UK 2014). In the U.S., lung cancer is the third most common cancer after prostate and breast cancer, and the lifetime risk for lung cancer is estimated at 6.9% (National Cancer Institute 2014).
U.S. annual incidence and mortality rates of lung cancer are 72.2 and 63.3 per 100,000, respectively, in males, and 51.1 and 39.2 per 100,000, respectively, in females (National Cancer Institute 2014). In Canada, the lifetime probability of lung cancer is 1 in 12 for men and 1 in 14 for women, which is closely echoed by the lifetime probability of dying from lung cancer, 1 in 13 for men and 1 in 17 for women (Canadian Cancer Society's Advisory Committee on Cancer Statistics 2014). 2014 incidence and mortality rates in Canada are predicted to be 58.5 and 47.2 per 100,000, respectively, in men, and 47.7 and 35.6 per 100,000, respectively, in women (Canadian Cancer Society's Advisory Committee on Cancer Statistics 2014).
As evident by the high mortality to incidence rate ratios (~0.8), lung cancer is a deadly disease and is among the cancers with the lowest 5-year relative survival rates – only 16.8% in the U.S. (National Cancer Institute 2014) and in Canada, 14% and 20% in men and women, respectively (Canadian Cancer Society's Advisory Committee on Cancer Statistics 2014). The statistics presented above are age-adjusted rates in the general population and not among smokers specifically.
Cigarette smoking is the leading risk factor for lung cancer, with 80 to 90% of all lung cancer cases attributable to cigarette smoke exposure. In the United Kingdom (U.K.), 86% of all lung cancer cases in 2010 were estimated to be caused by smoking, 83% due to active smoking and 3% due to environmental tobacco smoke exposure among nonsmokers. Before cigarette smoking became widespread, lung cancer was a rare disease. However, a relationship between tobacco use and nose cancer was noted as early as 1761 in the publication “Cautions against the immoderate use of snuff”. In the 1900s an increasing number of studies reported an association between smoking and lung cancer including a report on spousal second hand smoke as a cause of lung cancer among non-smoking women and a report on the correlation between increased tobacco sales and the increasing prevalence of lung cancer. Recognition of tobacco smoking as a cause of lung cancer and disease gained momentum after 1950 following three landmark epidemiology studies linking smoking and lung cancer.
As with many cancers, increasing age is associated with lung cancer risk and the median age of diagnosis is 70 years. Recent lung cancer screening trials relied on smoking and age to target high risk individuals for early detection, but additional prediction models have been developed, which also include other environmental exposures, family history, and respiratory disease. Family history of lung cancer in a first-degree relative, especially a sibling, is associated with an increased risk of lung cancer among both smokers and never smokers. Radon is the leading cause of lung cancer in non-smokers and the second leading cause in smokers. Other exposures identified as risk factors include asbestos, outdoor air pollution, occupational exposures (especially among those in rubber manufacturing, iron and steel founding and painting), drinking water with high levels of arsenic, exposure to ionizing radiation, indoor burning of coal, and environmental tobacco smoke. Previous lung disease (such as emphysema, tuberculosis, chronic bronchitis) and a weakened immune system (e.g. HIV/AIDS) are also recognized as risk factors for lung cancer.
Fig. 1 Lung cancer risk factors.
Lung cancers are broadly classified as small cell carcinomas and non-small cell carcinomas; the latter includes two of the most prevalent histological subtypes of lung cancer, adenocarcinoma and squamous cell carcinoma. While the prevalence of the histological subtypes of lung cancer have shifted over time, currently adenocarcinoma and squamous cell carcinoma are the most prevalent, overall and within smokers, consisting of approximately 40% and 20% of lung cancers within the United States, respectively.