Epidemiology

Lung cancer is the most common cancer worldwide and the second most common in the UK, with 41 000 new cases per year (13% of all new cancer diagnosis). The majority (87%) are in people over 65 years, with the highest incidence between 80 and 84 years and the lowest in people under 40. There has been a demographic shift, with the incidence and mortality rates falling in males and rising in females. Despite government initiatives to reduce smoking rates, lung cancer remains the biggest cause of cancer deaths in the UK and USA.

Aetiology

The most significant risk factor for lung cancer is smoking (80–90% of cases, RR = 17), including passive smoking (RR = 1.5). The risk is proportional to the patient’s pack years (packs smoked per day × years smoked), the age they started and the type of cigarette smoked. Other recognised risk factors include previous radiotherapy to the chest, and occupational exposure to chemicals such as asbestos, acetaldehyde, beryllium, cadmium, chromium, formaldehyde, polycyclic aromatic hydrocarbons, nickel and inorganic arsenic compounds.

There is a 2.5-fold increased risk of lung cancer where there is a significant family history, despite their own smoking history, and rarely lung cancers develop in patients with germ line mutations in genes such as in Rb and TP53.

Pathophysiology

Small cell lung cancer (SCLC) accounts for 20% of all lung cancers and arises in the larger airways; it tends to be a more central tumour. Most patients present with systemic disease and it frequently metastasises, via haematogenous spread, to the liver, skeleton, bone marrow, brain and adrenal glands. The small cells contain dense neurosecretory granules which can produce ectopic biological substances resulting in Cushing’s syndrome (ACTH) and SIAD. Mutations in RB1 and TP53 are found in 80% of patients with SCLC and abnormal DNA methylation of the cyclin D2 gene is common.

Non-small cell lung cancers (NSCLC) (80% of lung cancers) arise from the epithelial cells of the lung from the central bronchi to the terminal alveoli. They can be divided into three main types.

• Squamous cell carcinoma
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