What is the role of the exposure to carcinogens in the pathophysiology of non–small cell lung cancer (NSCLC)?

Updated: Jun 05, 2020
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Answer

Tobacco smoke contains more than 300 harmful substances with at least 40 known potent carcinogens. Polyaromatic hydrocarbons and nicotine-derived nitrosamine ketone (NNK) are known to cause DNA damage by forming DNA adducts in animal models. Benzo-A-pyrine also appears to induce molecular signaling such as AKT, as well as inducing mutations in p53 and other tumor suppressor genes.

The most common occupational risk factor for lung cancer is exposure to asbestos. Studies have shown radon exposure to be associated with 10% of lung cancer cases, while outdoor air pollution accounts for perhaps 1-2%. [7] In addition, preexisting nonmalignant lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and tuberculosis have all been shown to be associated with increased lung cancer rates.

The current multiple hit theory suggests that a series of toxic cellular insults disrupts orderly genetic reproduction. Symptoms ultimately develop from the uncontrolled disorganized growth that interferes with local or distant anatomy or physiologic processes. [7]

A study by Ito et al assessed the shift in histologic types of lung cancer in Japan and the United States in relation to the shift from nonfiltered to filtered cigarettes. [8] The study determined that the shift in cigarette types only altered the most frequent type of lung cancer, which shifted from SCC to adenocarcinoma.


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