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Lung Cancer: Overview and Risk Factors

Lung cancer is the most common cause of cancer death for men and women worldwide. It is the most frequently occurring cancer in men and the third most frequent in women. Lung cancer usually develops within the epithelium of the bronchial tree and subsequently invades the pulmonary parenchyma. In advanced stages, it invades surrounding organs and may metastasize throughout the body.

The most common histological types are:

Epidermoid (squamous cell) carcinoma (about 40% of lung cancer cases). This is the most common form, located centrally in the lung. The carcinoma arises from a dysplastic epithelial focus in one of the bronchi, presenting the cytological and nuclear features of atypia. Eventually, it invades the pulmonary parenchyma.

Adenocarcinoma (about 25% of cases). The lesions are peripheral or central, arising from the epithelium of small airways and showing evidence of glandular activity (sometimes producing mucin). Adenocarcinomas have a characteristic growth pattern along the alveolar septa, without destroying the underlying lung architecture.

Small cell (oat cell) carcinoma (about 20% of cases). This form involves the wall of a major bronchus, arising from specialized neuroendocrine cells (K cells) in the lungs, which show extensive mitotic activity and foci of necrosis. The tumor is commonly a central, perihilar mass. Virtually all small cell cancers are attributable to tobacco use.

Large cell (undifferentiated) carcinoma (about 15% of cases). This is a bronchogenic tumor with large pleomorphic cells containing prominent nucleoli. The cells are poorly differentiated and metastasize early.

Risk Factors

Tobacco smoking accounts for approximately 90% of lung cancers. Initially, tobacco smoke irritates the bronchial epithelium and paralyzes the respiratory cilia, depriving the respiratory mucosa of its defense and clearance mechanisms. The carcinogens in tobacco smoke then act on the epithelium, giving rise to atypical cells, which form the first stage of cancer: carcinoma in situ. After metaplastic transformation, the cancer invades bronchial and pulmonary tissues, and subsequently metastasizes hematogenously or via lymphatics. Additional risk factors include:

Passive smoking. Epidemiologic evidence suggests an increased risk of approximately 20% to 25% in nonsmokers regularly exposed to secondhand smoke.1

Occupation. Regular exposure to manipulated asbestos (1 of 5 deaths is due to lung cancer), chromium and nickel (heavy metals), benzopyrene, acroleine, nitrous monoxide, hydrogen cyanide, formaldehyde, nicotine, radioactive lead, carbon monoxide, insecticides or pesticides containing arsenic, glass fibers, and coal dust increases workers’ risk of bronchopulmonary cancer.

Family history. Investigations show a 14–fold higher frequency of lung carcinomas in smokers with a family history of lung cancer.2 Risk is also increased in individuals with Li–Fraumeni syndrome, resulting from an inherited mutation in the p53 gene.3

Immunosuppression. The risk of oncogenesis increases with conditions that weaken the immune system (eg, immunosuppressive medications, diseases, or malnutrition).

Air pollution. The mortality rate from lung cancer is 2 to 5 times higher in industrialized areas than in less polluted rural areas.

Inflammation. Chronic and recurrent respiratory diseases act as chronic irritants and play an oncogenic role (eg, tuberculosis, chronic bronchitis, recurrent pneumonias).

Ionizing radiation. Radiation exposure (x–rays, radon gas) increases carcinogenic risk in dose–dependent manner. Lung cancer is 10 times more frequent in uranium miners than in the general population.

Diet and nutrition. See Nutritional Considerations.


Lung Cancer: Diagnosis >>