Incidence and epidemiology

Primary lung cancer remains the most common malignancy after non-melanocytic skin cancer, and deaths from lung cancer exceed those from any other malignancy worldwide [ 1 ]. In 2012, lung cancer was the most frequently diagnosed cancer in males with an estimated 1.2 million incident cases worldwide. Among females, lung cancer was the leading cause of cancer death in more developed countries and the second leading cause of cancer death in less developed countries [ 1 ]. The highest incidence is found in Central/Eastern Europe and Asia with age-standardised incidence rates of 53.5 and 50.4 per 100 000, respectively. European projections for 2017 indicate a 10.7% drop in 5 years with an incidence of 33.3/100 000 in males and a rise of 5.1% and an incidence of 14.6/100 000 in females [ 2 ]. Contrary to the United States, the death rate in females is increasing in Europe [ 3 ]. The number of lung cancer-related deaths in Europe for 2017 is estimated to represent the leading cause of cancer deaths in both genders, accounting for 24% in males and 15% in females, respectively [ 2 ].

Non-small cell lung cancer (NSCLC) accounts for 80%–90% of lung cancers, while small cell lung cancer (SCLC) has been decreasing in frequency in many countries over the past two decades [ 4 ]. During the last 25 years, the distribution of histological types of NSCLC has changed: in the United States, squamous cell carcinoma (SCC), formerly the predominant histotype, decreased, while adenocarcinoma has increased in both genders. In Europe, similar trends have occurred in men, while in women, both SCC and adenocarcinoma are still increasing [ 5 ].

The World Health Organization (WHO) estimates that lung cancer is the cause of 1.59 million deaths globally per year, with 71% of them caused by smoking. Tobacco smoking remains the main cause of lung cancer and the geographical and temporal patterns of the disease largely reflect tobacco consumption during the previous decades. Both smoking prevention and smoking cessation can lead to a reduction in a large fraction of lung cancers [ 6 ]. In countries with active tobacco control measures, the incidence of lung cancer has begun to decline in men and is reaching a plateau for women [ 1,7-9 ]. Several other factors have been described as lung cancer risk factors, including exposure to asbestos, arsenic, radon and non-tobacco-related polycyclic aromatic hydrocarbons. Hypotheses about indoor air pollution (e.g. coal-fuelled stoves and cooking fumes) are made for the relatively high burden of non-smoking-related lung cancer in women in some countries [ 10 ]. There is evidence that lung cancer rates are higher in cities than in rural settings but many confounding factors other than outdoor air pollution may be responsible for this pattern.

About 500 000 deaths annually are attributed to lung cancer in lifetime never-smokers [ 1 ]. Absence of any history of tobacco smoking characterises 19% of female compared with 9% of male lung carcinoma in the United States [ 11,12 ]. An increase in the proportion of NSCLC in never-smokers has been observed, especially in Asian countries [ 13 ]. These new epidemiological data have resulted in ‘non-smoking-associated lung cancer’ being considered a distinct disease entity, where specific molecular and genetic tumour characteristics have been identified [ 14 ].

Use of non-cigarette tobacco products such as cigars and pipes has been increasing. A pooled analysis highlighted the increased risk, particularly for lung and head and neck cancers, in smokers (former and current) of cigars and pipes [ 15 ].

Familial risk of lung cancer has been reported in several registry-based studies after careful adjustment for smoking [ 16 ]. A recent study estimated the heritability of lung cancer at 18% but many of the genetic components remain unidentified. Genome-wide association studies (GWAS) have identified lung cancer susceptibility loci including CHRNA3, CHRNA5, TERT, BRCA2, CHECK2 and the human leukocyte antigen (HLA) region [ 17-19 ]. Another trial, including data from 29 266 cases and 56 450 controls from European descent, found 18 susceptibility loci reaching genome-wide significance, among which 10 were previously unknown. Interestingly, while four of the latter were associated with overall lung cancer risk, six were associated with lung adenocarcinoma only [ 20 ].

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